Breast Cancer in the News
On Judah Folkman and Avastin
The very miracle that gives us life can also take it away. This is what Dr. Judah Folkman discovered when he realized the mechanism of angiogenesis. Angiogenesis: the creation of a new blood supply from cells within the body. The most beautiful of angiogenesis is a fetus. The most deadly is found in cancer.
Two polar opposites, that which gives life and that which takes it away, are both developed through angiogenesis.
When Dr. Folkman made his discovery, over two decades ago, the world thought the key to unlocking the door that stops cancer had been found. However, it was not so easy. Creating an anti-angiogenesis drug proved difficult if not impossible. Until Avastin (Bevacizumab) hit the oncology world. It showed in clinical trials that it stops cancer cells from creating their own blood supply, thus stopping cancer from growing.
It was paired with other chemotherapies and there were some very good outcomes along with some deadly side effects, for some. However, it did work on women who had advanced breast cancer. It also showed promise in the treatment of early stage disease. I personally know women who benefited from this drug. It represented the future of cancer care. Until now.
This week, the FDA is considering pulling it from the market because studies show "not enough benefit compared to the risk when paired with current chemotherapies." Women who are currently benefiting from this drug will lose their insurance coverage for Avastin if the FDA succeeds in pulling this drug.
Avastin is a powerful weapon in the arsenal against breast cancer. If the FDA does not feel it works well with current, well established chemotherapies, they should have a warning for practitioners and patients alike. But they must not close the door for its use for future drugs that it may work extremely well with. One example is the new hope that is being found in Parp Inhibitors for triple negative disease. There has not been sufficient testing of Parp i, nor has there been combination trials of Avastin with these future drugs to completely rule out this hope for women who are desperate for a therapy that will extend their lives.
Pull Avastin from the market? The FDA should ask the women whose metastatic disease is now stable because of it before they close yet another door on survival. If Dr. Folkman were still alive today, he would most likely agree.
FDA May Pull Avastin From Market
Molly Peterson, BLOOMBERG News
Roche Holding AG’s top-seller Avastin may shed $1 billion in annual revenue if U.S. regulators follow a panel recommendation to revoke approval of the drug for use in breast cancer.
Scientific advisers to the Food and Drug Administration voted 12-1 yesterday to rescind Avastin’s clearance in breast cancer after finding the drug paired with chemotherapies didn’t work better than other medicines alone. The agency usually follows panels’ advice, though it isn’t required to do so.
Roche, Europe’s largest drugmaker, won FDA approval of Avastin for breast cancer in 2008 under an accelerated review that required the company to conduct trials proving the drug, with $5.97 billion in sales last year, slows progression of the disease. Tests failed to meet this goal, the FDA panel found. Withdrawal of U.S. approval could trim as much as $1 billion from annual sales by 2015, said Sanford C. Bernstein & Co. analyst Tim Anderson, in a report yesterday after the vote.
“Given the overwhelming majority against Avastin, we think there is a good chance the FDA will follow the committee’s advice,” Anderson said. He projected worldwide Avastin sales of about $6.5 billion this year, including approximately $1.2 billion from breast cancer. Eliminating U.S. breast cancer sales may cut Roche’s earnings a share by about 5 percent, he said.
No Expanded Use
Panelists also rejected Roche’s application to expand use of Avastin in breast cancer for pairings with more varieties of chemotherapy. Wider use from that approval could have pushed global breast-cancer revenue for Avastin to about $3 billion a year, said Martin Voegtli, an analyst with Kepler Capital Markets in Zurich, in a telephone interview yesterday before the panel vote.
“We are disappointed by the committee’s recommendation and believe Avastin should continue to be an option,” Sandra Horning, head of clinical development hematology/oncology at Roche said in an e-mailed statement today. “We will continue to discuss the data from the more than 2,400 women who participated in three phase III studies with the FDA.”
Roche, based in Basel, Switzerland, fell 6 Swiss francs, or 4.2 percent, to 137 francs at the 5:30 p.m. close of trading in Zurich. The stock declined 4.2 percent, the most in more than a year, July 16 after a FDA report concluded Avastin didn’t slow breast tumors in new studies as much as in earlier tests used to win approval.
“It is clear that the FDA do not believe Avastin adds a clinically meaningful benefit to patients,” said Dominic Valder, a London-based analyst with Evolution Securities, in a July 19 research report.
Sept. 17 Decision
“Today’s advisory committee vote does not change the current availability of Avastin for women with advanced breast cancer,” Charlotte Arnold, a spokeswoman for Roche’s South San Francisco, California-based Genentech unit, said yesterday in an e-mailed statement. The FDA will make a final decision by Sept. 17, she said.
Avastin is the first medicine to fight cancer by blocking the growth of blood vessels that feed tumors, a process called angiogenesis. It targets a chemical signal known as vascular endothelial growth factor, or VEGF. The treatment, also approved for brain, lung and colon tumors, costs about $50,000 a year. Avastin was developed by the company’s Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.
Most Common Malignancy
Breast cancer is the most common malignancy in females and strikes about 1 million women a year globally, according to the Geneva-based World Health Organization. Avastin is approved for about three quarters of women whose breast cancer has been recently diagnosed as having spread to other organs. It doesn’t include women who have a mutation to the HER2 protein, a known risk factor. Patients with HER2 mutations are eligible for another Roche drug, Herceptin.
The FDA’s 2008 clearance of Avastin for breast cancer overruled an advisory panel that concluded the benefit of slowing the spread of tumors wasn’t worth the risk of side effects including high blood pressure and death.
Approval was based on a clinical trial, called E2100, which showed Avastin slowed the spread of breast cancer by an additional 5.5 months when paired with paclitaxel chemotherapy, compared with the other drug alone, the FDA said in its report.
One trial completed since then, called Avado, showed that a high dose of Avastin paired with docetaxel chemotherapy extended the time patients lived without their disease worsening by 0.9 months, compared with treatment with chemotherapy alone, the FDA report said. A lower dose of Avastin gave patients 0.8 months.
Extended Life
A second trial finished after approval, called Ribbon-1, found Avastin combined with taxane or anthracycline-based chemotherapies stalled tumor growth by 1.2 months, compared with treatment with chemotherapy alone, the agency said in its review. Patients who got Avastin combined with Xeloda lived 2.9 months longer without their disease progressing, compared with chemotherapy alone.
“We have a far more comprehensive picture here of the role of Avastin than we had in 2008,” said Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, told the panel before yesterday’s vote.
Drugs that win conditional clearance through the FDA’s accelerated-approval program can later be pulled from the market if subsequent data fails to show that a treatment increases long-term survival or slows progression of the disease while improving quality of life.
‘Overwhelming Majority’
While Avastin is expensive and doesn’t work as well as early trials suggested, the “overwhelming majority” of breast cancer specialists think the drug has a use in certain patients, Jack Scannell, a Bernstein analyst in London, said in a July 15 research note.
Breast-cancer patients may lose insurance coverage for Avastin if the FDA revokes approval of the treatment, said Francisco Esteva, a professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.
“Even if we wanted to use it, patients would have to consider that it’s a very expensive therapy,” Esteva said July 15 in a telephone interview. “Without insurance support, I don’t think patients would be able to take it.”
WHAT IF...?
We have written several articles, blog posts and shared too many personal stories to take this anymore. Women are not getting early screening for breast cancer and that means their cancers are being found too late. They are found spread to lymph nodes and distant organs - found too late to treat - too late to do anything that could be prevented.
We do NOT have a cure yet. Until then, it is up to US, to take the pledge and save the lives of women who do not even know they have breast cancer: Because early detection is our ONLY DEFENSE.
Are you ready? Take the Before Forty Initiative Pledge!
Mammogram uproar as pols, doctors reject guidelines
Originally published: July 11, 2010 6:32 PM Updated: July 11, 2010 9:42 PM By DELTHIA RICKS
Eight months ago, a federal advisory panel triggered an uproar by saying most women needed fewer mammograms and should begin them at a later age. Today, the confusion over those guidelines has intensified as physicians and lawmakers demand they be withdrawn.
The recommendations suggested women without risk factors for breast cancer could wait until 50 to start annual screening. Within a day of their release, Health and Human Services Secretary Kathleen Sebelius issued a statement saying the guidelines didn't represent government policy, and advised women to "do what you've always done."
But the guidelines from the U.S. Preventive Services Task Force, a panel of outside experts chosen by HHS, are still posted on an official government website run by Health and Human Services although they have been modified slightly to say women between 40 and 49 who want a mammogram should get one if their doctor recommends it.
Still, the furor over the guidelines will not go away.
Sen. David Vitter (R-La.) wrote to Sebelius in May saying passage of the Patient Protection and Affordable Care Act in December required that the government withdraw the guidelines.
Vitter said the bill, passed by a bipartisan vote, called on HHS to remove the recommendations from its website and "cease all promotion of the November 2009 recommendations related to breast cancer screening and mammography"
In his letter, he wrote: "The fact that these recommendations are still being presented to the general public as 'current' is only serving to further confuse women on this critical issue. The recommendations were ill-conceived from the start. . . . They represent a step backward in our fight against a horrible disease."
Vitter spokesman Joel DiGrado said they have yet to receive a reply from Sebelius. "The senator's office has not heard anything back from HHS. This is not all that untypical for an agency. Their responses to formal letters can take quite some time."
Newsday made several attempts to get HHS to address the status of the guidelines - whether the agency still endorses them now that they've been edited, or whether they will be withdrawn, as some lawmakers are seeking. The agency did not provide answers to the questions and no one from HHS would address whether scrapping the guidelines is seriously under discussion.
Dr. Christine Hodyl, director of breast surgery at South Nassau Communities Hospital in Oceanside, said she never took the guidelines seriously - they're unrealistic for Long Island.
"This week alone," she said recently, "I operated on two women. One was 37 and the other was 41. Here on Long Island, the breast cancer rate is so high I tell women to get their baseline [first mammogram] at 35 to 40. If these [two] women had waited until 50, the cancer would have metastasized."
Another critic, Dr. Brian O'Hea, director of the Carol M. Baldwin Breast Care Center at Stony Brook Medical Center, said he never stopped recommending routine screening at age 40. "We're still in line with the American Cancer Society and have not changed a bit," O'Hea said.
Last month, a Harvard mammography expert charged that the guidelines are based on faulty science and should be retracted.
None of the task force members were experts in breast cancer or mammography.
Health care insurers, such as Empire BlueCross Blue-Shield and Vytra, say they are sticking with the cancer society's recommendations.
http://www.newsday.com/news/health/mammogram-uproar-as-pols-doctors-reject-guidelines-1.2096878
There is now proof that the US Task Force has done damage. This group of people announced in the fall that women under 50 years of age do not need mammograms. The No Surrender Breast Cancer Foundation is vehemently against this decision and has made our opinion known.
Our Before Forty Initiative is working hard to get the word out to all women that Early Detection is your BEST defense. If you want the highest chance of beating cancer: find it while it is still small. That is why we are educating women about the importance of baseline screenings BEFORE the age of Forty and follow-up care that involves not only mammography, but ultra sound and breast MRI.
We need your help to help us save the lives of women.
Please see our BEFORE FORTY INITIATIVE HERE.
Please DONATE to our foundation to help us. We need funding.
Read today's news, and you will find more proof why it is our duty to protect the women who come after us.
Mammogram screening down 13 percent since 'flawed' recommendations
By Aimee Heckel Camera Staff Writer
Posted: 06/23/2010 09:14:36 AM MDT
Read more: Mammogram screening down 13 percent since 'flawed' recommendations - Boulder Daily Camera http://www.dailycamera.com/lifestyles/ci_15351198#ixzz0ri8xRW5J
DailyCamera.com
Terry Stiven, of Lafayette, almost didn't get the test.
She had no family history of breast cancer. She'd had mammograms in the past, and she had no signs of cancer.
Then, this fall, the United States Preventative Service Task Force released new recommendations: Women between 40 and 49 years old don't need mammograms. The benefits of testing don't outweigh the risks, the task force said.
Now, it seemed there was no reason to get the 10-minute, slightly uncomfortable screening. In February, Stiven, 46, went ahead and got tested anyway, expecting nothing.
She had cancer.
Not invasive breast cancer, though. Doctors removed the lump, and she had four weeks of radiation. The experience was frightening, but not damaging.
Today -- just four months later -- Stiven is cancer-free, with extremely low chances of it returning. She still has both breasts, she runs triathlons and her life expectancy has not been shortened.
"If I'd waited four years, I don't know if I would have been alive," she says.
Stiven is one reason of many that local doctors have launched an aggressive campaign to counter the U.S. Preventative Task Force's advisory.
"Getting a mammogram is one of the most important things a woman can do to live a long, healthy life," says David Oppenheimer, the chief physician of the mammography department of the Boulder Community Hospital.
And he's not just talking about women older than 50.
One third of women diagnosed with breast cancer in Boulder County are between 40 and 49 years old, according to the Boulder Community Hospital. More than 40 percent are younger than 50 -- the task force's "arbitrary" age cut-off, Oppenheimer says.
Since the task force's recommendation, the hospital's imaging department reports a 13 percent decline in mammograms -- the majority among women in their 40s and 50s.
Nanna Bo Christensen, the Boulder Community Hospital's Breast Health Navigator, attributes this drop at least in part to the national recommendation.
Other women may be afraid they can't afford it -- even though it is illegal in Colorado for insurance companies not to cover screenings for women age 40 and older. The Women's Wellness Connection offers financial support for women who need it, too, says Christensen.
"Mammography saves lives," she says. "The key to survival is early detecting."
In fact, the younger the woman, the faster the breast cancer grows, doctors say, due to higher levels of estrogen, which feeds the cancer cells.
And if you find cancer before it spreads to the lymph nodes, Oppenheimer says, doctors have a 97 percent chance of curing it. Once it hits the lymphs, the cure rate plunges.
The number of women who die from breast cancer is down since 1990, and experts say that's primarily due to increases in the number of women being screened.
So why would a government panel recommend against something that statistics show helps save lives?
The task force looked at false-positive tests and the related anxiety, unnecessary biopsies and exposure to radiation.
Oppenheimer asserts data used for the recommendation was scientifically flawed, and that the task force left out several important studies to skew the numbers in favor of its recommendation. As to the radiation question, he says about 1 in 3 million mammograms actually causes cancer.
"However, we know that one in eight women are going to get breast cancer in their lives, so the advantages far outweigh the tiny risk," he says.
Mammograms detect cancer 90 percent of the time, the hospital says, making them the most effective screening tool.
A slew of organizations have since denounced the recommendation, including the National Cancer Institute, the American Cancer Society, the Susan G. Komen Breast Cancer Foundation, Avon Foundation, the Obama Administration, American College of Radiology, American Society of Breast Imaging, American College of Obstetricians and Gynecologists.
"Now we as physicians and a health care community have a huge job on our hands to re-educate the community," Oppenheimer says. "Once people stop getting tested, it's a huge effort to convince people to start again."
The U.S. task force also said women older than 50 only need to get a mammogram every two years instead of annually.
When Jill Kamon, of Boulder, heard that, she says she was horrified.
Kamon was diagnosed at age 51 with breast cancer. If she had followed the recommendations, she would have skipped the mammogram that found the small lump in the back of her breast. The cancer would have had a year to grow before her next mammogram. She couldn't feel it with a self-exam.
"To me, the mammogram and radiologist who read the mammogram completely saved my life. There is no question," says Kamon, who had a double mastectomy in the summer of 2007. The lump was only 6 millimeters big, but it was growing aggressively.
"I'd had a mammogram exactly one year earlier that was clear," she says. "That dot was not there."
By the numbers
13 percent -- Decrease in mammograms at the Boulder Community Hospital since the U.S.
Preventative Service Task Force recommendation in the fall. The majority of these women are in their 40s and 50s.
30 percent -- Decrease in breast cancer's death rate since 1990, nationally.
42 percent -- Of women diagnosed with breast cancer at the Boulder Community Hospital were younger than 50; 32 percent were in their 40s.
More than 30 percent -- Decreased death rate, due to mammography screenings for women in their 40s.
One in eight -- American women are affected by breast cancer.
97 percent -- Chance of curing breast cancer if it's caught before spreading to the lymph nodes.
About 1 in 3 million -- Chance of the radiation from a mammogram causing breast cancer.
Sources: Boulder Community Hospital, Susan G. Komen for the Cure.
Important information for Tamoxifen Users
OncologySTAT has released this very important discussion about CYP2D6 enzyme and tamoxifen. Be aware that there are drugs you may be taking that could render Tamoxifen powerless, leaving you vulnerable for breast cancer recurrence.
Dr. Matthew P. Goetz: Tamoxifen Metabolism, Endoxifen, and CYP2D6 Polymorphism
2010 Jun 15, Interview by L Scott Zoeller
Please go to THIS LINK for more information.
Get moving after breast cancer surgery...
See our post surgical exercises HERE
Exercise Preserves Freedom of Movement After Breast Cancer Surgery
Washington, June 16 (ANI): A study has found that exercise can help patients maintain shoulder movement and minimize loss of arm or shoulder function after breast cancer surgery.
The new Cochrane review found exercise programs needed to be created to help patients who have just had surgery, as most survivors develop pain, shoulder stiffness and arm swelling after treatment.
Physicians usually prescribe arm and shoulder exercises after surgery to prevent pain and stiffness in those areas on the side of the cancer, but the problems often persist for years.
"There has been some concern that too much aggressive movement soon after surgery might cause pain, delay healing, and increase the risk of arm swelling," said lead review author Margaret McNeely, an assistant professor of physical therapy at the University of Alberta and clinical researcher at the Cross Cancer Institute, in Canada.
McNeely's team examined 24 research studies comprising 2,132 women with a confirmed breast cancer diagnosis and who had undergone surgery such as a radical mastectomy, modified radical mastectomy, or a local wide excision or lumpectomy.
They had also all had surgery removing lymph nodes from the axilla, or armpit, to determine the extent of the cancer.
Specially designed programs included range-of-motion movements for the shoulders and stretching exercises.
The review showed that starting exercise early after surgery, within the first to third day, might result in better shoulder movement in the early weeks following surgery.
"However, starting exercise that soon after surgery may cause more wound drainage and require drains to remain in place longer than if exercise is delayed by about one week," McNeely said.
The Cochrane Collaboration, an international organization that evaluates medical research, published the review.
Fourteen studies compared the effect of structured exercise to usual care, in which women received an exercise pamphlet or no exercise instruction at all.
Of these, structured programs including physical therapy regimens in the early postoperative period led to a significant improvement in shoulder range of motion over the short and long term.
"Several persistent complications can greatly diminish a patient's quality of life," said Douglas Blayney, M.D., medical director at the University of Michigan's Comprehensive Cancer Center.
Blayney said that although current surgical treatment is attempting to move away from disturbing the axilla, more women, especially younger women, are choosing mastectomy over breast conserving surgery.
"Combined, these trends in primary treatment of breast cancer make this review highly relevant," said Blayney, who has no affiliation with the review.
Nevertheless, he noted that making suitable exercise programs widely available to breast cancer patients in a timely manner would be a challenge.
He said optimal breast cancer care now involves a team with a wide range of health specialists: surgeons, radiation oncologists, medical oncologists, reconstructive surgeons and others.
"This review demonstrates that early involvement of a new team member who manages exercise or physical therapy is also useful for the best outcome," he said.
"Implementation of modern primary treatment strategies - - including early intervention with suitable exercises - should reduce the incidence of these heartbreaking complications," Blayney added. (ANI)
Sequential seems superior...
Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast Cancer
N Engl J Med. 2010 Jun 3;362(22):2122-2124, SM Swain, JH Jeong, CE Geyer Jr, JP Costantino, ER Pajon, L Fehrenbacher, JN Atkins, J Polikoff, VG Vogel, JK Erban, P Rastogi, RB Livingston, EA Perez, EP Mamounas, SR Land, PA Ganz, N Wolmark
ABSTRACT
In this study that enrolled more than 5000 women with early-stage, node-positive, operable breast cancer, chemotherapy with sequential-ACT improved both DFS and OS when compared with four cycles of doxorubicin/docetaxel...
Background: Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.
Methods: We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.
Results: At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.
Conclusion: Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status.
Liver Mets? Consider Surgery
Liver Resection for Multimodal Treatment of Breast Cancer Metastases: Identification of Prognostic Factors
Ann Surg Oncol. 2010 Jun 1;171546-1554, K Hoffmann, C Franz, U Hinz, P Schirmacher, C Herfarth, M Eichbaum, MW Büchler, P Schemmer
In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.
STUDY IN CONTEXT
The role of liver resection (LR) is controversial as a component of multimodal therapy for hepatic metastases (HM) associated with breast cancer. Thus, a better understanding of the benefits and clinical outcomes of the surgical approach is needed, along with identification of the potential prognostic factors for long-term survival.
To this end, Hoffmann et al. retrospectively evaluated data that were prospectively collected for 41 patients with hepatic breast cancer metastases. All of these patients underwent exploratory laparotomy for LR. Of the 41 patients, 40 patients had primary tumor adenocarcinoma, and 1 patient had a mucinous carcinoma of the breast. Patients selected for hepatic resection were stable, having no more than five metastases and with extrahepatic metastases under remission. No vascular invasion was evident, and R0 resection was deemed possible. Karnofsky index was ≥80%.
The median time from treatment of the primary breast tumor to diagnosis of HM was 3.4 years (interquartile range [IQR], 1.2–8.0 years). Segment resections were performed in 19 patients (45%) and major hepatectomy was performed in 22 patients (right hemihepatectomy, 25%; left hemihepatectomy, 12%; extended right hemihepatectomy, 7%; extended left hemihepatectomy, 9%).
The primary outcome measure was overall survival from the date of LR. Secondary outcome parameters were disease-free survival, progression-free survival, and recurrence-free survival from the date of LR and overall survival from the date of primary breast tumor operation.
Median follow-up was 34 months after LR (IQR, 8–68 months). The estimated median survival was 58 months. The 3- and 5-year survival rates after LR were 68% and 48%, respectively, although they were 80% and 59%, respectively, from the time of diagnosis of HM, with an estimated median survival of 79 months. The 5-, 10-, and 15-year survival rates after treatment of the primary tumor were 84%, 76%, and 50%, respectively, with a median survival of 211 months. Incidence of HM earlier than 12 months after treatment of the primary tumor (5-year overall survival, 28%) was associated with a three-times-higher likelihood of mortality (hazard ratio, 3.8) compared with HM occurring later than 1 year after treatment of the primary tumor (5-year overall survival, 58%). R0 resection resulted in 3- and 5-year survival rates of 80% and 62%, respectively, while patients after R1/R2 resection had a median survival of 28 months after LR, with patients six times more likely to die compared with patients after R0 resection (hazard ratio, 6.3).
In the absence of extrahepatic metastases at the time of LR, the 3- and 5-year overall survival rates were 75% and 59%, respectively, compared with rates of 51% and 31%, respectively (P = 0.15), for patients who did have extrahepatic metastases.
Following R0/R1 resection, patients without extrahepatic disease at the time of LR (n = 26) had an estimated median disease-free survival of 34 months; the 3- and 5-year disease-free survival rates were 46% and 31%, respectively, with HM reducing the respective rates to 26% and 13%.
The median time to intrahepatic recurrence in patients without extrahepatic disease at the time of LR was 8.6 months; the 3- and 5-year intrahepatic recurrence-free survival rates were 71% and 62%, respectively.
The results of this study showed that, in patients with hepatic breast cancer metastases (without any type of peritoneal carcinomatosis and/or positive hilar lymph nodes), LR was safe and improved long-term survival. No perioperative deaths occurred during this study.
Check that label first...
Some sunscreens contain dangerous chemicals
June 4, 2010 3:10 PM
By MCCLATCHY-TRIBUNE
We all know it's important to use sunscreen. But it's also important to check the label for ingredients that are safe for you and the environment.
The Environmental Working Group, a nonprofit public health and environmental research and advocacy organization based in Washington, D.C., studied nearly 1,000 brand-name sunscreens in 2009. Three in five did not adequately protect skin from the sun or contained harmful chemicals.
One controversial sunscreen ingredient is oxybenzone. It absorbs ultraviolet light, but research shows it also can be absorbed through the skin. The Centers for Disease Control and Prevention released a study in 2008 showing that 97 percent of Americans it tested were contaminated with oxybenzone.
Oxybenzone is allowed in sunscreens, but recent research has linked it to allergies, hormone disruption and cell damage that can lead to skin cancer. It's bad for the environment, too. Researchers believe oxybenzone, once washed down the drain or off swimmers' bodies, contributes to the feminizing of certain species of male fish in our oceans, rivers and lakes.
So why is oxybenzone still considered "safe" in sunscreens? Unfortunately, the Federal Drug and Food Administration, which regulates sunscreen safety, has not updated mandatory sunscreen standards in more than 30 years.
What should you do? Look for a broad-spectrum sunscreen that offers protection from both UVA and UVB rays but does not contain oxybenzone.
Sunscreens containing zinc oxide or titanium oxide are recommended by the Environmental Working Group.
Emerging studies show that we are out of balance with too much Omega 6 verses the healthy Omega 3s. Extra virgin olive oil helps us regain that balance. Stay away from other fats and processed foods and you will not only feel the difference, but you will see it, too.
Breast Cancer Survivors Lose More Weight On Olive-Oil Enriched Diet
04 Jun 2010
Researchers from The Miriam Hospital have found that olive oil may offer another potential health benefit - it produces greater weight loss in breast cancer survivors compared to a more traditional low-fat diet.
The findings may be of significance to women with breast cancer, since excess weight at the time of diagnosis, or even moderate weight gain during cancer treatment, is associated with an increased risk of cancer recurrence, particularly in post-menopausal women.
In this pilot study, women followed two 1,500-calorie diets - a conventional low-fat diet recommended by the National Cancer Institute (NCI) and a plant-based olive oil diet similar to the Mediterranean diet. After eight weeks on each diet, participants selected one diet to follow for an additional six months of continued weight loss or weight management.
According to the findings, published in the June issue of the Journal of Women's Health, 80 percent of women who started with the plant-based olive oil diet lost more than 5 percent of their baseline weight, compared to 31 percent who started with the NCI diet. But researchers were most surprised to find that after trying both diets, most women chose to stick with the less conventional, higher fat olive oil diet, saying they found the food more appetizing, accessible and affordable.
Mary Flynn, PhD, RD, LDN, the study's lead author and a research dietitian at The Miriam Hospital, says many breast cancer patients don't realize there is a link between weight and cancer recurrence.
"That's why it was important for us to compare these two diets and determine which one the women not only enjoyed following, but also produced the best weight loss, because that's the diet they're more likely to stick with," says Flynn. "In this case, it was a diet enriched with extra virgin olive oil, which is a source of healthy fats, and includes foods associated with improving one's health, such as vegetables, beans and other plant products."
Extra virgin olive oil has been associated with decreasing breast cancer risk in Greece, Spain and Italy, where it is consumed in great quantities. Many studies have also demonstrated the cancer protective properties of carotenoids, a phytonutrient found in the red, orange and yellow pigments of fruits and vegetables. The NCI lists obesity as a risk factor for disease recurrence but does not recommend a specific diet for weight loss, although it has consistently recommended lowering dietary fat to prevent breast cancer.
Flynn developed the olive oil diet used in the study, which included at least three tablespoons of olive oil per day, with nuts at breakfast. Women also ate three servings of fruit and unlimited vegetables daily, and whole grains were also emphasized. Women could eat limited amounts of poultry and fish per week but red meat and polysaturated fats, like vegetable oils, were prohibited.
Because the NCI-recommended low-fat diet is not as specific, women had a less restrictive meal plan. Their diet consisted of at least five servings of fruits and vegetables, approximately 25 to 50 grams of fat (including canola oil) and six to seven ounces of lean meat (not red meat) daily.
The study included 44 overweight women (BMI of at least 25) diagnosed with invasive breast cancer after the age of 50 who were within four years after completing treatment. The order of the diets was randomly assigned, and participants followed each diet for eight weeks. Women were provided with meal plans and recipes for each diet and were asked to keep three-day food diaries at weeks four and eight of each diet and during months three and six of the follow-up period. Weight was measured and blood samples were taken at the end of each study period.
Overall, 28 of the 44 women completed both diets and 19 of the 22 eligible for the six months of follow-up chose to follow the plant-based olive oil diet. All 19 women either maintained their weight loss or lost additional weight during this time.
"I found this surprising, particularly since the low-fat diet is more commercial and more recognizable to women, so I thought the preference would be more evenly split," says Flynn, who is also an assistant professor of medicine at The Warren Alpert Medical School of Brown University. "But the women who enjoyed the olive oil diet said not only were they losing weight but they weren't as hungry. That's because they were advised to include fat in the form of olive oil or nuts at each meal, so they weren't as likely to snack between meals, which can cause weight gain."
As researchers expected, the plant-based olive oil diet also resulted in lower triglycerides (a type of fat found in the blood) and higher high-density lipoprotein cholesterol (HDL, or "good" cholesterol). High triglycerides and low levels of HDL have both been linked with increased cancer risk.
The study was supported by a grant from The Susan G. Komen for the Cure Foundation. Steven E. Reinert, MS, from Lifespan Information Services, was co-author on the study.
Source: Lifespan
Copyright: Medical News Today
Scientific Proof helps us promote our Before Forty Campaign...
Breast Cancer Screening: MRI Sensitive, No Added Value With Mammography, Study Suggests
ScienceDaily (Mar. 8, 2010) — Do we need a revision of current recommendations for breast cancer screening? According to a recent prospective multicenter cohort study published in the Journal of Clinical Oncology, this appears advisable at least for young women carrying an increased risk of breast cancer. The results of the EVA trial confirm once more that magnetic resonance imaging (MRI) is substantially more accurate for early diagnosis of breast cancer than digital mammography or breast ultrasound: MRI is three times more sensitive for breast cancer than digital mammography.
For the EVA trial, almost 700 women were enrolled. Aim of the trial was to refine existing guidelines for surveillance of women at high and moderately increased risk of breast cancer. Findings suggest that in these women, MRI is essential for early diagnosis -- and that a mammogram or an ultrasound examination does not increase the "cancer yield" compared to what is achieved by MRI alone. Researchers conclude that annual MRI is not only necessary, but in fact sufficient for screening young women at elevated risk of breast cancer. In women undergoing screening MRI, mammograms will have no benefit and should be discontinued. Moreover, MRI screening is important not only for women at high risk, but also for those at moderately increased risk.
Between 2002 and 2007, the EVA trial recruited 687 women who carried a moderately increased risk of breast cancer (lifetime risk of 20% and over). Women underwent 1679 screening rounds consisting of annual MRI, annual digital mammography and half-annual screening ultrasound examinations. During this time span, 27 women received a new diagnosis of invasive cancer or DCIS (Ductal Carcinoma In Situ).
Of all imaging methods under investigation (digital mammography, ultrasound and MRI), MRI offered by far the highest sensitivity: MRI identified 93% of breast cancers. 37% of cancers were picked up by ultrasound. The lowest sensitivity was achieved by digital mammography, which identified only one-third of breast cancers (33%). These results confirm once more that MRI is essential for surveillance not only of women at high risk, but also for women at moderately increased risk of breast cancer. Moreover, the results contradict current guidelines according to which mammography is considered indispensable for breast cancer screening. One aim of the EVA trial was to question this concept and to ask whether it is still appropriate to require that MRI should only be used in addition to mammography. The results speak for themselves: If an MRI is available, then the added value of mammography is literally negligible. Researchers conclude that MRI is necessary as well as sufficient for screening young women at elevated risk of breast cancer. Since mammography appears to be unnecessary in women undergoing MRI, its use is no longer justifiable, and current guidelines should be revised to reflect this.
Current guidelines questionable
Current guidelines for women at high familial risk of breast cancer recommend annual MRI (with or without ultrasound) and annual MRI starting at age 25-30. "These guidelines were set up based on little or no scientific evidence, and mainly reflect expert opinion," summarizes Prof. Christiane Kuhl, radiologist at the University of Bonn and principal investigator of the EVA trial. "In the light of the results of the EVA trial, such recommendations should be revisited." This seems even more important because digital mammography uses x-rays (ionizing radiation) to detect breast cancer. "The radiation dose associated with regular mammographic screening is clearly acceptable and safe," underscores Kuhl. "However, regular mammographic screening usually starts at age 40-50." The situation is different if systematic annual mammographic screening is started at age 25-30. "Not only because these women will undergo more mammograms and therefore will experience a cumulative lifetime radiation dose that will be substantially higher, but also because the breast tissue of young women is more vulnerable to the mutagenic effects of radiation." This appears to be especially true for BRCA mutation carriers. "Accordingly, we impose more radiation on less radiation-tolerant breast tissue -- for a very limited, if any, diagnostic benefit." Therefore, Kuhl advocates a revision of existing guidelines: "It is no longer justifiable to insist on annual mammographic screening women in their thirties if they have access to screening MRI."
MRI is a mature technology
In the past, MRI was used strictly in addition to mammography only. The allegedly high rate of "false positive" diagnoses and the allegedly insufficient sensitivity for DCIS were the main reason to discourage its use as a stand-alone method for breast cancer screening. "In this multicenter trial, with basic quality assurance implemented not only for mammography, but also for MRI, we were able to prove that false positive diagnoses are avoidable if MRI studies are interpreted with adequate radiologist expertise." In the EVA cohort, the Positive Predictive Value achieved with MRI was already even higher than that of mammography or breast ultrasound. "Moreover, we found that MRI offered the highest sensitivity especially for DCIS," adds Dr. Kuhl. "It is simply wrong to state that we need a mammogram to detect intraductal cancer."
Kuhl et al. Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial. Journal of Clinical Oncology, 2010; DOI: 10.1200/JCO.2009.23.0839
Targeted therapy for TNBC...this could be big
This could be big. Breast cancer is not one disease as we all know. Triple Negative Breast Cancer has been on the back burner in terms of new therapies, until now. PARP treatment is changing the future of metastatic TNBC patients. Now, a new, targeted therapy has identified a sub-type of TNBC tumors...
New Subtype of Breast Cancer Responds to Targeted Drug
ScienceDaily (Mar. 2, 2010) — A newly identified cancer biomarker could define a new subtype of breast cancer as well as offer a potential way to treat it, say researchers at Washington University School of Medicine in St. Louis.
Their findings will be published in the March 1 online early edition issue of the Proceedings of the National Academy of Sciences.
The research could further refine what recent breast cancer research has concluded: that breast cancer is not one disease, but many. So far, research has firmly established that at least five subtypes of breast cancer exist, each having distinct biological features, clinical outcomes and responses to traditional therapies.
The biomarker identified by the Washington University researchers is found frequently in breast cancers and especially in those that have poorer outcomes. It stems from overactivation of a gene called LRP6 (low-density lipoprotein receptor-related protein 6), which stimulates an important cell-growth signaling pathway. LRP6 can be inhibited by a protein discovered in the same laboratory, which could become an effective drug against the breast cancer type, the researchers say.
"We found increased expression of the LRP6 gene in about a quarter of breast cancer specimens we examined, and we think LRP6 overexpression could be a marker for a new class of breast cancer," says Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. "In addition, we found that this biomarker is often associated with breast cancers that are either harder to treat or more likely to recur. We already have an agent that seems to be effective against LRP6-overexpressing tumors, which could someday become a therapy for tumors that right now have few treatment options."
The research was conducted primarily by Chia-Chen Liu, a graduate student in the Bu lab, who is a fellow in the Cancer Biology Pathway Program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.
The researchers' analysis of human breast cancer tissue samples found significant increases in LRP6 levels in 20 percent to 36 percent of the tumors. LRP6 was increased more frequently in ER (estrogen receptor)-negative or HER2 (human epidermal growth factor receptor 2)-negative samples. LRP6 was also increased more frequently in so-called triple-negative breast tumor samples, which test negative for ER, HER2 and PR (progesterone receptor).
In general, patients who have triple-negative breast cancers have an increased risk of disease recurrence after initial treatment and a poorer prognosis. Furthermore, although ER-positive and HER2-positive tumors can be targeted with specific therapies, ER-negative and HER2-negative tumors cannot. So it appears that LRP6 overexpression is often associated with tumors that are currently difficult to treat, says Bu.
Research in the lab had earlier discovered a protein that binds to and inhibits LRP6. This study showed that the protein, called Mesd (mesoderm development), was able to slow the growth of breast cancer cells in the laboratory and to inhibit mammary tumor growth in laboratory mice.
Importantly, mice treated with Mesd did not experience any of the known side effects, such as bone lesions, skin disorders or intestinal malfunctions, associated with inhibition of this growth pathway.
"Our work introduces Mesd as a promising antitumor agent that might be further developed for breast cancer therapy," Bu says. "It would be analogous to such successful breast cancer therapies as Herceptin (trastuzumab), which specifically targets HER2-positive breast cancer."
The researchers also found that a small segment of Mesd has the same effect as the larger molecule. This segment, or peptide, is more stable than the whole protein molecule and can be easily synthesized.
The researchers have patented the protein and the peptide through the university's Office of Technology Management. Recently, Raptor Pharmaceutical Corp. licensed Mesd from the university to develop it for clinical use.
Funding from the National Institutes of Health and the Siteman Cancer Center supported this research.
Got Hope? TNBC patients do now!
The Reviews Are in:
Blockbuster drug known as PARP = A future of hope
"I believe that in the next two to three years, PARP inhibitors will do for triple-negative breast cancer what trastuzumab [Herceptin] did for HER2 breast cancer." Jenny Chang, Baylor
"This development may have the potential to change patient survival . . . and appears to potentially change the natural history of at least a subclass of metastatic breast cancer [TNBC]" Clifford Hudis, MSK
“When you go home, be excited. Be really excited about this. Tell your patients there is reason to be hopeful.” Eric Winer, Dana Farber
Until now, the treatment for triple negative breast cancer has been limited. The options for metastatic patients were few and far between. Until now. The first completed studies of PARP, have shown that not only does it slow progression of disease, but patients are experiencing a complete response to the drug.
The side effects of PARP are generally well tolerated and do not include hair loss.
Where once there was no hope, no magic drug for triple negative patients, PARP is proving itself to be, as Dr. Jenny Chang, of the Baylor School of Medicine said, “What Herceptin did for HER2 breast cancer.”
“Many experts have argued that it is not possible to change survival in stage IV breast cancer. Certainly now there evidence for an alternative viewpoint; that with the use of very effective drugs, we can change overall survival, and we should aim for that." Clifford Hudis, MSK
For more information, speak to your oncologist. For information on recruiting trials for PARP click the following links:
http://clinicaltrials.gov/ct2/show/NCT00664781?term=PARP&rank=3
http://clinicaltrials.gov/ct2/show/NCT00516724?term=PARP&rank=4
http://clinicaltrials.gov/ct2/show/NCT00647062?term=PARP&rank=6
Sources:
Chang C. Interview with Neil Love. in Conversations with Oncology Investigators - Bridging the Gap between Research and Patient Care. Breast Cancer Update 2009;8(6):3-6 [Track 5; with audio].
Hudis C. Interview by L Scott Zoeller 2009 Oct 21. Extended Survival With PARP Inhibitors Changes Expectations in Metastatic Breast Cancer. Viewpoints. In OncologySTAT 2009.
Carlson R. PARP Inhibitors Show Promise Against Metastatic Triple-Negative Breast Cancer in Early Studies. Oncol Times 2009;31(15):10-11.
Genomic project zeroes in on TNBC...
Triple Negative Breast Cancer News: Genome Project
Background: Drug companies have developed an array of drugs to attack cancer and other conditions influenced by genetics, but it’s difficult to tell which patients will respond to which drugs.
What’s happening: A new study will sequence the genomes of cancer tissue from 14 breast cancer patients whose tumors have progressed despite multiple treatments.
The future: Proponents of “genomic medicine” think it will become increasingly possible to use sequencing to steer individual patients to the drugs most likely to work.
A Carlsbad biotechnology company is helping launch an unusual cancer study that may eventually lead to doctors tailoring treatments to patients’ genes. Life Technologies says the study — involving sequencing the genomes of 14 patients with a tough-to-treat form of breast cancer — is a step toward a future of “genomic medicine,” a decade after the sequencing of the first human genome.
It’s evidence of how quickly work in this area is progressing, with the $2.6 billion that went into the Human Genome Project reduced to $6,000 per genome on Life Technologies’ latest sequencing instrument. “This is a pretty amazing example of how far these tools of genomics are moving into direct patient applications,” said Jeffrey Trent, president of the Phoenix-based Translational Genomics Research Institute, which is working with Life Technologies on the project.
The company will announce the study today to coincide with the opening of a two-day conference on genomic medicine in La Jolla, at which experts will discuss the latest breakthroughs and the outlook for more advances in the field. Already, biotechnology research has created numerous drugs that target genetic problems that lead to cancer and other conditions. In the case of breast cancer, at least a dozen such drugs are on the market, said Dr. Daniel
D. Von Hoff, physician-in-chief at the translational genomics institute. A big problem, however, is that it’s difficult to predict which drugs will work for a particular patient. That’s where sequencing is supposed to help.
“For those mutations for which we do have drugs, we can help the physician make more informed decisions than they’re making today,” said Linh Hoang, director of personalized medicine at Life Technologies.
The study could also help scientists identify promising areas to explore for future drugs. It’s impossible to know ahead of time whether the 14 patients have genetic patterns that current drugs address, but researchers will also look for similarities in the DNA of the 14.
“It may lead to more targets that pharmaceutical companies will want to design drugs around,” Hoang said.
The study will involve patients with what’s known as triple-negative breast cancer whose tumors have progressed despite multiple therapies. That type of cancer makes up about a fifth of breast cancer cases and doesn’t respond to common drugs, such as Herceptin. Patients will be enrolled by U.S. Oncology, a Houston-area company that specializes in cancer-treatment services, and Von Hoff said the plan is to take the first 14 people who meet the study criteria.
A spokeswoman for U.S. Oncology said the company plans to enroll patients from about a half-dozen of its sites with the highest incidences of triple-negative cases. Sites in Colorado, Oregon, Texas and Virginia have already been identified.
Tissue samples will be obtained through noninvasive surgery, Von Hoff said. Then the patients will go home to await sequencing results that should be produced within a few weeks.
The idea is to then direct them to appropriate treatment, but Von Hoff declined to predict in how many cases that will be possible. “We don’t know,” Von Hoff said. “We do know there are more and more drugs out there for patients who have mutations.”
There have been other studies that sequenced disease tumors, most notably an ongoing government effort known as the Cancer Genome Atlas that aims to produce comprehensive genetic maps of at least 20 types of cancer.
What separates the new study is its attempt use the data to drive treatment strategies, not merely to collect information “It’s a different question,” the genomics institute’s Trent said. “This is a study about how we’re going to start to use this in a precision medicine approach.”
A big effort will go into “bioinformatic” analysis, which Von Hoff said will involve a trillion pieces of data per patient. Hoang said one project in lung cancer found 30,000 mutations.
In coming years, scientists expect the cost of sequencing to decline and the sophistication of the tools to improve to the point that sequencing becomes more viable as a diagnostic device.
Hoang said Life Technologies expects the cost of the reagent chemicals that it sells, which enable genome sequencing, to drop from $6,000 to $3,000 by the end of the year. “This is really laying the foundation for a future that may take five or 10 years to materialize,” Hoang said. “But it is truly groundbreaking.”
THOMAS KUPPER, UNION TRIBUNE, Uniontrib.com
When to Consider prophylactic bilateral mastectomy...
Contralateral Prophylactic Mastectomy Associated With Survival in Select Breast Cancer Patients
ScienceDaily (Mar. 3, 2010) — Contralateral prophylactic mastectomy (CPM), a preventive procedure to remove the unaffected breast in patients with disease in one breast, may only offer a survival benefit to breast cancer patients age 50 and younger, who have early-stage disease and are estrogen receptor (ER) negative, according to researchers at The University of Texas M. D. Anderson Cancer Center.
Published online February 25 in the Journal of the National Cancer Institute, it's the first population-based study to find an association between the procedure and survival in any group of breast cancer patients. The findings should offer evidence to both the women making this often agonizing decision and the physicians responsible for their care.
According to Isabelle Bedrosian, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology, a growing number of breast cancer patients are opting for the procedure; recent statistics have shown that the rate of CPM in women with stage I-III breast cancer increased by 150 percent from 1998 to 2003 in the United States.
"In our clinic, we've seen a dramatic increase in the number of women requesting CPM, and across the breast cancer community, studies have shown that the utilization of the procedure is skyrocketing," said Bedrosian, the study's co-corresponding author. "Until now, we've counseled these patients on a very important, personal decision in a vacuum. With our study, our goal was to understand the implications of the surgery and who may benefit."
For the retrospective, population-based study, the researchers used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry now representing 26 percent of the country's population, to identify 107,106 breast cancer patients who underwent a mastectomy for treatment, as well as a subset of 8,902 women who had CPM. All of the women were treated for stages I -- III breast cancer between 1998 and 2003. Patients were stratified for ER status, stage of disease and age. Breast cancer-specific survival served as the study's primary endpoint.
Rigorous analysis was paramount in the design of the study, said George J. Chang, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology.
"It was important to take a critical eye and look at all the different ways the data could be misinterpreted to ensure that biases were not impacting our findings," said Chang, the study's co-corresponding author. "Using multi-variable analysis as well as risk stratification, we did our analysis in many different ways -- through SEER, comparing the survival of these patients to that of the general population, as well as examining non-cancer related versus cancer-specific survival. All alternative analyses resulted in the same conclusion; we found one group for whom this surgery offers a true survival benefit."
The researchers found a clear survival benefit for a select group of women that represents less than 10 percent of the breast cancer population. Those younger than age 50 with stage I or II cancer with ER negative disease had a survival benefit of 4.8 percent at five years. However, both Bedrosian and Chang expect that future research will show increased survival benefit with longer follow-up in the population, as a patient's likelihood of getting a second breast cancer increases with time.
While the findings should serve as a guideline for breast cancer patients and their physicians to have an informed, medically-based discussion about CPM, they do not determine that CPM is medically inappropriate for all others with the disease, said the researchers.
"Our research found that breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM," said Bedrosian. "However, there are other populations -- such as women between the age of 50 and 60 -- where the findings about the procedure remain less clear. In addition, for young women with early stage, estrogen receptive positive breast cancer who receive Tamoxifen for only five years, we really do not know whether they would derive a life-long protective effective from a second breast cancer event. Therefore, for some additional breast cancer patients, CPM may very well be a medically-appropriate option."
In addition, the researchers note, the study captured neither family history nor BRCA status; it also did not include DCIS, or stage 0 breast cancer patients.
In addition to Bedrosian and Chang, Chung Yuan Hu in the Department of Surgical Oncology, also authored the all-M. D. Anderson study.
Pomegranate Therapy...
Natural Compounds in Pomegranates May Prevent Growth of Hormone-Dependent Breast Cancer
ScienceDaily (Jan. 6, 2010) — Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.
"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.
Previous research has shown that pomegranate juice -- punica granatum L -- is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.
Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.
After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.
"We were surprised by our findings," said Chen. "We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different."
According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.
"This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells," said Stoner, who is not associated with this study. "It's not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet."
Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.
Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner's sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.
"More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention," Brown said. "This study does suggest that studies of the ellagitannins from pomegranates should be continued."
Until then, Stoner said people "might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs."
DCIS News
Trial Launched to Test New Treatment for Pre-Invasive Breast Cancer
ScienceDaily (Mar. 2, 2010) — Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That's what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI) are trying to prove.
In January, the IBCI and CAPMM launched the PINC Trial, short for Preventing Invasive Breast Neoplasia with Chloroquine. This three-year clinical trial will test the effectiveness of the anti-malarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal.
With an estimated 254,650 patients diagnosed in 2009 alone, breast cancer is the most common form of cancer in women according to statistics by the American Cancer Society. Approximately one quarter of those patients will have DCIS. Many more women are being diagnosed with DCIS, non-invasive breast cancer, with the routine use of screening mammography.
According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing pre-invasive cancer cells using a novel therapy with chloroquine, which has been used to treat malaria in the past.
"We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In pre-clinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. "What this trial is proposing is to treat DCIS patients with chloroquine, an autophagy blocker before they receive standard of care surgery to treat their DCIS disease. We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS. We may be able to prevent someone from needing a mastectomy and offer them breast conserving surgery."
Once patients have consented and enrolled, the size of their breast tumor will be measured through a non-invasive imaging technique called magnetic resonance imaging (MRI). Tissue samples will be taken from patients by Inova's doctors and transported to CAPMM for analysis. The PINC trial will combine chloroquine with Tamoxifen depending on the patient's tumor profile. After treatment, the MRI will be repeated to see if the tumor has shrunk and the patient will then proceed with surgery and follow up therapy.
What made the researchers think to use a malaria drug to treat breast cancer? According to Ginny Espina, a CAPMM research assistant professor, it works by starving the cancerous cells.
"Pre-cancerous cells have adapted to survive inside the milk duct without a blood supply and with very few nutrients. They overcome starvation through a process called autophagy. It's a way for a cell to make its own food and store it in a 'cookie jar.' In the breast ducts, the DCIS cells use these 'cookies' to survive and potentially spread. Simply put, chloroquine goes into the cell's 'cookie jars' and prevents the cells from using that food so that they eventually die from starvation," says Espina.
Of note, researchers are also using chloroquine in patients with unique types of brain tumors.
The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy.
"I think the most exciting thing is that we are able to offer women a new clinical trial using a well tolerated therapy in a new way to help prevent the development of invasive breast cancer and hopefully, ultimately, it will keep them from needing any additional treatment or surgery," says Edmiston. "We look forward to a future where all breast cancer can be prevented or destroyed."
The clinical study is being funded by George Mason University and Inova Health System. This study is based on scientific findings made under a Department of Defense funded breast cancer grant to George Mason University (Lance Liotta MD, PhD) in partnership with Inova.
Her2 News...
Neoadjuvant Chemotherapy With Trastuzumab Followed by Adjuvant Trastuzumab Versus Neoadjuvant Chemotherapy Alone, in Patients With HER2-Positive Locally Advanced Breast Cancer (the NOAH Trial)
Lancet. 2010 Jan 30;375(9712):377-384, L Gianni, W Eiermann, V Semiglazov, A Manikhas, A Lluch, S Tjulandin, M Zambetti, F Vazquez, M Byakhow, M Lichinitser, MA Climent, E Ciruelos, B Ojeda, M Mansutti, A Bozhok, R Baronio, A Feyereislova, C Barton, P Valagussa, J Baselga
Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer.
EXPERT COMMENTARY
Lee Schwartzberg, MD, Editor-in-Chief Oncology Stat
In HER2-positive breast cancer, adding trastuzumab to chemotherapy yields impressive benefit in both the adjuvant and metastatic setting and is the standard of care. The current trial fills in the gaps by providing randomized clinical trial evidence of a 41% improvement in event-free survival when trastuzumab was given to patients with HER2-positive locally advanced or inflammatory breast cancer in the neoadjuvant setting. Particularly noteworthy in this NOAH trial was the use of every-3-weeks dosing of trastuzumab from initiation of treatment, a low cardiac event rate despite concurrent adriamycin/trastuzumab therapy, and a marked benefit recorded in the inflammatory breast cancer group of a 73% improvement in event-free survival.
ABSTRACT
Background: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.
Methods: We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.
Findings: Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61–78; n=36 events] with trastuzumab, vs 56% [46–65; n=51 events] without; hazard ratio 0•59 [95% CI 0•38–0•90]; p=0•013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.
Interpretation: The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.
Copyright © Elsevier Inc. All rights reserved
PARP Props...
PARP Inhibition Could Have Broad Application
Elsevier Global Medical News February 2010
Lee Schwartzberg is Senior Partner and Medical Director, The West Clinic, Memphis, TN.
1. In your view, which development in breast cancer that has occurred in 2009 could have the most significant impact on oncology?
The development in 2009 with the potential for the most impact was the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors as a new class of agent for the treatment of malignancies. Reports this year confirmed both single-agent activity of PARP inhibitors and synergy with chemotherapy. Moreover, the benefit was highly significant, leading to better overall survival in one small randomized trial.1
2. What specific changes in oncology have you observed or do you foresee as a result of this development?
If results hold up, PARP inhibition will be the first systemic therapy designed for hereditary cancers that contain a somatic mutation responsible for the malignancy, specifically BRCA1 or BRCA2 mutations. Patients with these mutations lack functional BRCA proteins, which are important in normal DNA repair, and thus they develop cancers. More broadly, there is exciting evidence of benefit from PARP inhibition in triple-negative breast cancer, an aggressive subtype for which there is currently no specific therapy.
3. Could you put this development into historical perspective for the practicing oncologist?
While PARP enzymatic function as a DNA repair mechanism has been recognized for some time, what is new is the idea that inhibition of this pathway in cells where alternative repair systems (such as BRCA) have already been damaged could lead to cancer cell death. This concept is termed synthetic lethality. This could represent a paradigm shift leading to exploration of similar approaches in other critical cellular pathways.
4. Would you sum up in a single sentence why you chose this development as the top story of the past year?
PARP inhibition capitalizes on a central and critical function of malignant tissue, DNA repair, and has already shown strong evidence of benefit. This class of drugs could have broad application in treating other cancers as well.
Reference
1. O'Shaughnessy J, Osborne C, Pippen J, et al. Final results of a randomized phase II study demonstrating efficacy and safety of BSI-201, a Poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with gemcitabine/carboplatin (G/C)in metastatic triple-negative breast cancer (TNBC) (abstract 3122). Presented at 32nd San Antonio Breast Cancer Symposium 2009; San Antonio, TX; December 10-13, 2009.
© ONCOLOGYSTAT 2010
It's not you, it the treatment...
Decline in Breast Cancer Mortality Means Increase in Chronic Symptoms
Elsevier Global Medical News. 2008 Jan 17, B. Jancin
SAN ANTONIO (EGMN) - The other side of the impressive decline in breast cancer mortality during the last several decades is the unprecedented number of survivors with tough to control chronic symptoms caused by the disease or its aggressive therapy, Dr. Charles L. Loprinzi said at the San Antonio Breast Cancer Symposium.
He focused on evidence-based therapies of five of the most common and problematic breast cancer survivorship issues: vaginal dryness, fatigue, chemotherapy-induced neuropathy, diminished libido, and hot flashes.
Vaginal dryness: Pilocarpine shows enough promise that Dr. Loprinzi and colleagues have embarked on an ongoing randomized, double-blind, placebo-controlled trial of the oral drug at 5 mg once daily or b.i.d. in 192 women treated for breast cancer. Results should be available next year.
The impetus for the study was an anecdotal report a few years ago of marked clinical improvement in cyclophosphamide-induced vaginal dryness in four patients, along with a separate earlier report of significantly decreased vaginal dryness as a secondary outcome measure in a phase III trial of pilocarpine for oral and ocular dryness in patients with Sjögren's syndrome (Arch. Intern. Med. 1999;159:174-81). The drug is approved for that indication as well as for dry mouth caused by head and neck radiation therapy.
Estrogen therapy is effective for vaginal dryness and is worthwhile in some severely affected women, but there is concern that it could promote breast cancer recurrence. That concern extends to vaginal estrogens as well.
"All of the vaginal agents, in my mind, do lead to systemic levels of estrogen in some patients," said Dr. Loprinzi, professor of medicine and chair of oncology at the Mayo Clinic, Rochester, Minnesota.
Nonestrogenic vaginal lubricants are "somewhat effective," but are clearly inferior to estrogen in comparative studies, he added.
Fatigue: This is a major complaint for cancer patients across the full spectrum of disease, from those on adjuvant chemotherapy to patients with advanced, incurable cancer. Exercise is the intervention with the strongest evidence base.
"Exercise is the answer, not more rest," Dr. Loprinzi emphasized.
Modafinil, donepezil, L-carnitine, and methylphenidate have been looked at in pilot studies, but more work is needed before any of them can be recommended for cancer-related fatigue.
Similarly, Dr. Loprinzi and coworkers were encouraged by the results of their pilot 8-week, double-blind dose-finding study of American ginseng, in which roughly 25% of cancer patients on 1,000 or 2,000 mg/day of ginseng reported their fatigue was moderately to very much better, compared with 10% on placebo.
"The evidence isn't there to recommend ginseng for use at this time, but we're excited about it. The toxicity profile looked very favorable. We're about to start a larger placebo-controlled trial," the oncologist said.
Chemotherapy-induced neuropathy: Gabapentin is widely prescribed for this problem. However, the sole rigorous study to date - a multicenter, placebo-controlled, double-blind, crossover trial conducted by Dr. Loprinzi and colleagues in the North Central Cancer Treatment Group (NCCTG) - failed to demonstrate any benefit (Cancer 2007 Nov. 1;110:2110-8).
Vitamin E (alpha-tocopherol) at a dose of 400 mg/day was reported to protect against cisplatin-induced peripheral neuropathy and ototoxicity in an interim analysis of a 50-patient randomized, placebo-controlled study presented at last year's American Society of Clinical Oncology meeting. The NCCTG has an ongoing randomized trial, also comparing vitamin E at 400 mg/day and placebo. Until the results are in, Dr. Loprinzi urged caution in using vitamin E for prevention of chemotherapy-induced neuropathy.
"We haven't proved that it's helpful, number 1, and also there are some data suggesting that vitamin E can get in the way of cytotoxic therapy, particularly radiation therapy for the head and neck area. Maybe that will also apply to chemotherapy. We need to sort all this out," he said.
Low libido: Sexual counseling is the only thing that can be recommended. Transdermal testosterone cream proved ineffective in a double-blind, randomized, placebo-controlled crossover trial conducted by Dr. Loprinzi and the NCCTG (J. Natl. Cancer Inst. 2007 May 2; 99:672-9).
Testosterone did improve low libido in several prior studies in women without cancer. The most likely explanation for the disparate results lies in the fact that all participants in those studies were either premenopausal or on estrogen replacement therapy; in contrast, the cancer patients weren't receiving estrogen, he noted.
Hot flashes: Effective nonhormonal therapies are available. Dr. Loprinzi and his colleagues showed in a randomized, double-blind, placebo-controlled trial that venlafaxine at 37.5 or 75 mg/day reduced hot flash scores by 40% and 60%, respectively, from baseline (Lancet 2000; 356:2059-63).
In a subsequent double-blind, placebo-controlled crossover trial, they demonstrated that fluoxetine at 20 mg/day also was effective in reducing hot flashes in women with a history of breast cancer (J. Clin. Oncol. 2002;20:1578-83), although it appears to be less so than venlafaxine.
Paroxetine at 20 mg/day appears to be roughly as effective as venlafaxine at reducing hot flashes, based upon randomized controlled studies by other investigators. Sertraline at 50 and 100 mg/day doesn't seem to work as well as do the other antidepressants.
A couple of negative venlafaxine studies have been reported. However, neither featured adequate pretreatment baseline hot flash scores. That's a fatal methodologic flaw, according to Dr. Loprinzi, who noted that in his study that venlafaxine reduced hot flash scores by an average of 30% on day 1, compared with the baseline week.
Tamoxifen is metabolized by cytochrome P450 2D6 to a key active metabolite, endoxifen, which is believed to be responsible for the selective estrogen receptor modulator's efficacy in preventing breast cancer. Coadministration of paroxetine and tamoxifen has been reported to result in a significant decrease in plasma endoxifen levels (J. Natl. Cancer Instit. 2003;95:1758-64). In contrast, venlafaxine didn't reduce endoxifen levels in another study (Clin. Pharmacol. Ther. 2006;80:61-74).
Another nonhormonal option is gabapentin, which at 900 mg/day, significantly reduced hot flash scores in a placebo-controlled trial by investigators at the University of Rochester (Obstet. Gynecol. 2003;101:337-45).
Copyright © 2008 International Medical News Group
At last, they are coming to their senses...
New Mammogram Guidelines Issued ... Again
livescience.com Mon Jan 4, 3:16 pm ET
Breast cancer screening just got more confusing today, as two medical organizations announced annual mammograms should begin at age 40, and earlier for high-risk women. The recommendations contradict a recent advisory for less frequent screenings beginning at age 50, not 40.
The recommendations for less frequent mammograms, released in November, came from the U.S. Preventive Services Task Force, with panel experts saying they were responding to data showing routine mammograms starting at age 40 rarely saved lives and more often resulted in misdiagnoses that just fueled anxiety and debilitating treatment.
This new advice, which is published in the January issue of the Journal of the American College of Radiology, comes from the Society of Breast Imaging (SBI) and the American College of Radiology (ACR). And these groups suggest just the opposite - that the screening does save lives.
"The significant decrease in breast cancer mortality, which amounts to nearly 30 percent since 1990, is a major medical success and is due largely to earlier detection of breast cancer through mammography screening," said lead study author Dr. Carol H. Lee, a radiologist at Memorial Sloan-Kettering Cancer Center. "For women with the highest risk of developing breast cancer, screening technologies in addition to mammography have been adopted," said Lee, who is the chair of ACR's Breast Imaging Commission.
What's a woman to do? Regarding how women should follow the task force recommendations from November, Dr. Carl D'Orsi, director of Emory University's Breast Imaging Center, said, "As a bottom line, they should be ignored." D'Orsi was a member of the team that came out with today's recommendations.
Dr. Ned Calonge, chairman of the U.S. Preventive Services Task Force, had not responded to a request for an interview as of this writing.
Screening science
D'Orsi and his colleagues reviewed the results of several randomized trials in Europe and North America, which included nearly 500,000 women in total. The review of these studies showed a 26 percent reduction in breast cancer mortality.
"This is scientifically driven with data, unlike what the task force did," D'Orsi said.
While today's recommendations are consistent with those put out by other groups, including the American Cancer Society, the new ones include other imaging techniques in addition to mammography.
Here are some of the highlights:
The U.S. Preventive Services Task Force, an independent government agency made up of 16 primary care physicians and public health specialists, in November recommended breast cancer screening every other year for women aged 50 to 74. They argued against routine screening before this age.
That was counter to their own guidelines from 2002, D'Orsi said.
"All of a sudden, with no new data - ignoring the fact that there are seven trials that demonstrate a drop in breast cancer mortality with use of mammography versus no mammography, plus that breast cancer mortality has dropped 30 percent - they come out with a recommendation that no screening be done at age 40 to 49," D'Orsi told LiveScience.
He added, "Basically they said nothing is good. Just wait until it breaks through your skin and we'll take care of it. That's what we did in 1940."
In fact, the task force did note a 15-percent reduction in mortality among those ages 40 to 49 who are screened," D'Orsi and colleagues wrote in their research paper. But they stated the harms outweigh the benefits. These harms include: anxiety over false positive results, the screening itself, need for additional testing or biopsy, and the possibility of overdiagnosis and overtreatment.
Why start screening at age 50? Essentially, years ago scientists began grouping women under and over age 50 into separate groups. And so when the age groups get compared, there are far fewer incidences of breast cancer in the younger group than in those 50 and older.
"Of course there's more breast cancer there, because it's age dependent," D'Orsi said. "That doesn't mean you don't screen. As a matter of fact those cancers [in the younger age group] are biologically more significant and may have a greater impact on life expectancy."
November, 2009
Government Panel Urges Change in Age from 40 to 50 for Mammograms-
A response
To save money, to reduce insurance costs and to reduce "Anxiety" a panel that guides the ACS has declared that women should skip mammograms until the age of 50, and then only have them every other year or so... because they don't do any good.... they cause too much anxiety....they cost too much.
Not having screening and having your cancer found too late costs a lot of money, too. It causes anxiety that is beyond all compare. And they can't do any good because your cancer is already spreading.
This blog post is dedicated to the women we have lost, only very few had the genetic cancer link that is exempt from this murderous recommendation. Most of these women were diagnosed before the age of 40 or in their early 40s. None of them are alive today.
Stephanie
Lisa
Amy
Denise
Mena
Susan
Susie
Lani
Lori
Deb
Ferne
Kay
Dawn
Annie
Julie
Twilah
Helen
Jodi
Kari Lynn
Cindy
Erin
Kathy
Cheryl
Lisa
Laura
Mary Ellen
Mabel
Donna
Marge
Jacque
Kathy
Fran
Vicky
Carla
Chris
Shelley
Julie
Leah
Connie
Shelli
Jayne
Ruth
Elena
Jen
Peggy
Kelly
Stacey
Diane
Bev
Theresa
Luann
Donna
Kathy
Diane
Roza
Kelly
Felicia
Stacy
Mildred
June
Sadie
Ann
Emmaline
Sprite
Breezy
Kay
Kathleen
Lanie
Charlotte
Tine
Annette
Janie
Frances
Bluekitten
Momcasey
Janell
Jane
Shirl
Mary
Andee
LuAnn
Theresa
Linda
Faye
Marie
Roza
Linda
Flo
Kathy
Kat
Karen
Mavy
Raven
Cherieboop
Ann
Pam
Nancy
In Reversal, Panel Urges Mammograms at Age 50, not 40
By Gina Kolata
Most women should start regular breast cancer screening at age 50, not 40, according to new guidelines released Monday by an influential group that provides guidance to doctors, insurance companies and policy makers.
The new recommendations, which do not apply to a small group of women with unusual risk factors for breast cancer, reverse longstanding guidelines and are aimed at reducing harm from overtreatment, the group says. It also says women age 50 to 74 should have mammograms less frequently — every two years, rather than every year. And it said doctors should stop teaching women to examine their breasts on a regular basis.
Just seven years ago, the same group, the United States Preventive Services Task Force, with different members, recommended that women have mammograms every one to two years starting at age 40. It found too little evidence to take a stand on breast self-examinations.
The task force is an independent panel of experts in prevention and primary care appointed by the federal Department of Health and Human Services.
Its new guidelines, which are different from those of some professional and advocacy organizations, are published online in The Annals of Internal Medicine They are likely to touch off yet another round of controversy over the benefits of screening for breast cancer.
Dr. Dianna Petitti vice chairwoman of the task force and a professor of biomedical informatics at Arizona State University said the guidelines were based on new data and analyses and were aimed at reducing the potential harm from overscreening.
While many women do not think a screening test can be harmful, medical experts say the risks are real. A test can trigger unnecessary further tests, like biopsies, that can create extreme anxiety. And mammograms can find cancers that grow so slowly that they never would be noticed in a woman’s lifetime, resulting in unnecessary treatment.
Over all, the report says, the modest benefit of mammograms — reducing the breast cancer death rate by 15 percent — must be weighed against the harms. And those harms loom larger for women in their 40s, who are 60 percent more likely to experience them than women 50 and older but are less likely to have breast cancer, skewing the risk-benefit equation. The task force concluded that one cancer death is prevented for every 1,904 women age 40 to 49 who are screened for 10 years, compared with one death for every 1,339 women age 50 to 74, and one death for every 377 women age 60 to 69.
The guidelines are not meant for women at increased risk for breast cancer because they have a gene mutation that makes the cancer more likely or because they had extensive chest radiation. The task force said there was not enough information to know whether those women would be helped by more frequent mammograms or by having the test in their 40s. Other experts said women with close relatives with breast cancer were also at high risk.
Dr. Petitti said she knew the new guidelines would be a shock for many women, but, she said, “we have to say what we see based on the science and the data.”
The National Cancer Institute said Monday that it was re-evaluating its guidelines in light of the task force’s report.
But the American Cancer Society and the American College of Radiology both said they were staying with their guidelines advising annual mammograms starting at age 40.
The cancer society, in a statement by Dr. Otis W. Brawley, its chief medical officer, agreed that mammography had risks as well as benefits but, he said, the society’s experts had looked at “virtually all” the task force and additional data and concluded that the benefits of annual mammograms starting at age 40 outweighed the risks.
Other advocacy groups, like the National Breast Cancer Coalition, Breast Cancer Action, and the National Women’s Health Network, welcomed the new guidelines.
“This is our opportunity to look beyond emotions,” said Fran Visco, president of the National Breast Cancer Coalition. The task force “is an independent body of experts that took an objective look at the data,” Ms. Visco said. “These are the people we should be listening to when it comes to public health messages.”
Some women, though, were not pleased. “I know so many people who had breast cancer and survived, and what saved their lives was early detection,” Janet Doughty, 44, of San Clemente, Calif., said in a telephone interview. She said she had had an annual mammograms since her late 30s and would not stop now.
The guidelines are not expected to have an immediate effect on insurance coverage but should make health plans less likely to aggressively prompt women in their 40s to have mammograms and older women to have the test annually.
Congress requires Medicare to pay for annual mammograms. Medicare can change its rules to pay for less frequent tests if federal officials direct it to.
Private insurers are required by law in every state except Utah to pay for mammograms for women in their 40s.
But the new guidelines are expected to alter the grading system for health plans, which are used as a marketing tool. Grades are issued by the National Committee for Quality Assurance, a private nonprofit organization, and one measure is the percentage of patients getting mammograms every one to two years starting at age 40.
That will change, said Margaret E. O’Kane, the group’s president, who said it would start grading plans on the number of women over 50 getting mammograms every two years.
The message for most women, said Dr. Karla Kerlikowske, a professor in the department of medicine, epidemiology and biostatistics at the University of California, San Francisco, is to forgo routine mammograms if they are in their 40s.
Starting at age 50, Dr. Kerlikowske said, “the message is to get 10 mammograms in a lifetime, one every two years.” That way they get the most benefit and the least harm from the test. If women are healthy, she added, they might consider having mammograms every two years until age 74.
Nearly two-thirds of all women in their 40s had mammograms within the last two years, as did 72 percent of women age 50 to 65, according to an editorial by Dr. Kerlikowske that accompanies the report.
In order to formulate its guidelines, the task force used new data from mammography studies in England and Sweden and also commissioned six groups to make statistical models to analyze the aggregate data. The models were the only way to answer questions like how much extra benefit do women get if they are screened every year, said Donald A. Berry, a statistician at the University of Texas M. D. Anderson Cancer Center and head of one of the modeling groups.
“We said, essentially with one voice, very little,” Dr. Berry said. “So little as to make the harms of additional screening come screaming to the top.”
The harms are nearly cut in half when women have mammograms every other year instead of every year. But the benefits are almost unchanged.
The last time the task force issued guidelines for mammograms, in 2002, the report was announced by Tommy G. Thompson, the secretary of health and human services. When the group recommended mammograms for women in their 40s, some charged the report was politically motivated. But Dr. Alfred Berg of the University of Washington, who was the task force chairman at the time, said “there was absolutely zero political influence on what the task force did.”
It was still a tough call to make, Dr. Berg said, adding that “we pointed out that the benefit will be quite small.” In fact, he added, even though mammograms are of greater benefit to older women, they still prevent only a small fraction of breast cancer deaths.
Different women will weigh the harms and benefits differently, Dr. Berg noted, but added that even for women 50 and older, “it would be perfectly rational for a woman to decide she didn’t want to do it.”
Researchers worry the new report will be interpreted as a political effort by the Obama administration to save money on health care costs.
Of course, Dr. Berry noted, if the new guidelines are followed, billions of dollars will be saved.
“But the money was buying something of net negative value,” he said. “This decision is a no-brainer. The economy benefits, but women are the major beneficiaries.”
Scientists have found a faulty gene linked to half of all breast cancers which experts have hailed as the most important discovery in the disease since the 1970s.
Rebecca Smith, Medical Editor Published: 11:39AM BST 05 Oct 2009
The finding will help researchers understand how cancer develops and may in future lead to new treatments, they said.
Everyone is born with the gene, called NRG1, but in some people it gets damaged during their lifetime and this can lead to cancer developing, it has been found.
Damaged NRG1s have been found in half of breast cancers and it has also been implicated in half of all prostate and bowel cancers along with one quarter of ovarian and bladder cancers.
When the gene works properly it acts as a brake, stopping cancer cells from growing, but when it is damaged the brakes are off, allowing the cells to multiply into a tumour.
Everybody is born with an intact NRG1 but it gets damaged in some people during their lifetime, thereby enabling cancer to develop.
The exact reason why the gene is damaged is lost has not yet been discovered.
However, by identifying the gene, experts hope they will be able to target therapies at specific cancers in the future.
The discovery of NRG1 is the most significant step forward in cancer gene research since another gene, p53, was discovered in the 1970s and was later implicated in the development in cancer in the 1980s.
This was the first "tumour suppressor" gene found within cells and it is now known that p53 is faulty or inactivated in many cancers.
The discovery was described as a "major step forward" by cancer charities in working out how cancer develops.
Dr Paul Edwards, of the department of pathology at the University of Cambridge, who discovered the gene with colleagues, said it provided "vital information" about how some cancers spread.
He said: "I believe NRG1 could be the most important tumour suppressor gene discovery in the last 20 years as it gives us vital information about a new mechanism that causes breast cancer.
"We found the gene on chromosome 8 partly by good luck and partly by good judgment.
"In every case that we looked at where a big chunk of chromosome 8 had been lost, at least part of the gene was lost.
"The gene was effectively 'turned off' in a lot of breast cancers.
"If we have found the gene that is lost on chromosome 8 and we know that some other cancers also lose that bit of chromosome 8, then it is logical that it is the same gene.
"We have got strong evidence that the gene is implicated in breast cancer but we have no reason to think it's not the same for other cancers, including prostate and colon cancer."
The research was published in the journal Oncogene and funded by Breast Cancer Campaign and Cancer Research UK.
Arlene Wilkie, director of research and policy at Breast Cancer Campaign, said: "Knowing the identity of this gene will lead to far more detailed studies of how it works and how it is involved in breast cancer development.
"This research is a major step forward in understanding the genetics of cancer and could open up a host of new strategies to improve diagnosis and treatment.
"In the UK, 12,000 women die from this disease every year, so it is vital we understand how breast cancer develops in order to stop it happening."
Lesley Walker, director of cancer information at Cancer Research UK, said: "This discovery is an important step forward in understanding a disease that more than 45,500 women are diagnosed with in the UK each year.
"It might then be possible to develop ways to bypass the gene or target treatments to the defect."
Aromatase Inhibitors and Joint Pain: A Deeper Look
Nick Mulcahy
September 23, 2009 — One third of postmenopausal women with breast cancer taking aromatase inhibitors (AIs) reported arthralgia — either new onset or worsening, according to investigators of a new study published online September 14 in the Journal of Clinical Oncology.
This percentage of patients experiencing joint pain was "expected," according to an editorial accompanying the study.
However, the study authors did not stop at investigating the prevalence of AI-associated arthralgia.
Because "few studies" have investigated the morphologic changes in joints and tendons in patients with this pain, the study authors used sonographic and electrophysiologic measurements to take a look at the affected tissues.
Nevertheless, the new study does not authoritatively correlate the findings from sonography and electromyography with clinical findings, observes the editorialist, Rowan T. Chlebowski, MD, PhD, from the Los Angeles BioMedical Research Institute at Harbor UCLA Medical Center in Torrance, California.
For instance, patients in the study with AI-related arthralgia had more frequent electrophysiologic findings of carpal tunnel syndrome (46% vs 20%; P < .05) than those without arthralgia (including those taking and those not taking AIs).
However, this 49% incidence of carpal tunnel syndrome in patients with AI-associated arthralgia is much higher than when the syndrome is identified through clinical symptoms. In large clinical trials of AIs and tamoxifen, the incidence of carpel tunnel syndrome was less than 3% for patients taking the AIs, Dr. Chlebowski notes.
The authors of the new study acknowledge that "the real prevalence of carpel tunnel syndrome would have been different if the signs and symptoms [had] been taken into consideration."
Very few patients discontinue treatment because of arthralgia.
AI-associated arthralgia is a "substantial problem" and one in need of "improved interventions," Dr. Chlebowski writes.
However, the editorialist and the study authors agree that most joint pain associated with AIs is mild to moderate and is best managed with analgesics. "Very few patients discontinue treatment because of arthralgia," the authors note.
More Findings
In the study, 120 postmenopausal patients with stage I to III breast cancer were evaluated for anatomic changes in the joints, and inflammatory markers were compared by Turkish investigators, led by Omer Dizdar, MD, from Hacettepe University Institute of Oncology in Ankara.
The team found that a range of markers of inflammation, such as C-reactive protein, were comparable in the patients taking AIs and the control subjects, and in the study participants with and without arthralgia.
The study supports previous reports that autoimmune disease "does not play a role in the etiology of AI-associated arthralgias," observes Dr. Chlebowski.
With regard to anatomic changes, the investigators found that the patients often had changes in their affected joints and tendons. Women taking AIs (n = 92) had increased tendon thicknesses, which is associated with the syndrome, compared with a control group of women (n = 28) with breast cancer not receiving the therapy (P < .01). Patients with AI-related arthralgia had more frequent joint and tendon effusions than those without pain (69% vs 42%; P < .05).
"These findings suggest that increased tendon thicknesses in patients on AIs may reflect some form of tendinopathy secondary to AI use. Further damage to the tendons and synovium results in effusions in tendon sheaths in a subgroup of patients, which is translated as arthralgia clinically," the authors write.
Anatomical matters aside, both Dr. Chlebowski and the study authors believe that arthralgia in this setting is also related to hormonal factors to some degree. Both note that joint pain is also a problem in postmenopausal women, even without breast cancer. In the landmark Women's Health Initiative (WHI) study, 74% of women without breast cancer reported joint pain, writes Dr. Chlebowski.
Notes on Managing Arthralgias
This study does not change the basic approach of clinicians to arthralgia, says Dr. Chlebowski.
At present, oncologists should carefully observe their patients for development of this problem.
"At present, oncologists should carefully observe their patients for development of this problem, clearly express to their patients the benefits of continued adherence [to AIs], and provide the limited available therapies," he writes.
The limited therapies can include acupuncture; 1 small pilot study suggested benefit from a 6-week regimen, notes Dr. Chlebowski. Vitamin D supplementation is a question "considered open," he adds, explaining that 2 ongoing studies are evaluating high-dose supplementation for AI-associated joint pain. However, 2 other trials, including the WHI, did not show any benefit from the vitamin, he says.
Joint pain associated with AIs still does not have an "optimal management strategy," writes Dr. Chlebowski.
Nevertheless, he cites a recent expert panel's recommendation to use "high-dose nonsteroidal anti-inflammatory drugs or selective COX-2 inhibitors as initial short-term therapy . . . to address initial pain relief, with subsequent titration to minimum effective dosage" (Ann Rheum Dis. 2007; 66:377-388).
Dr. Chlebowski reports being a consultant to AstraZeneca, Novartis, and Pfizer, all of which market AIs, and receiving honoraria from AstraZeneca and Novartis. The study authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print September 14, 2009. Abstract, Abstract
Metformin is more effective than chemotherapy alone - Study supports cancer stem cells hypothesis
In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in the September 14 online first edition of Cancer Research, a journal of the American Association for Cancer Research.
"We have found a compound selective for cancer stem cells" said lead researcher Kevin Struhl, Ph.D ., the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at Harvard Medical School. "What’s different is that ours is a first-line diabetes drug"
These findings add to a growing body of preliminary evidence in cells, mice and people that metformin may improve breast cancer outcomes in people. In this study, the diabetes drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.
The results fit within the cancer stem cell hypothesis, an intensely studied idea that small subsets of cancer cells have a special power to initiate tumors, fuel tumor growth and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor.
"There is a big desire to find drugs specific to cancer stem cells" said Struhl. "The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It’s already [in use as] a first-line diabetes drug"
The possible usefulness of a diabetes drug against cancer lends credence to an emerging idea that, in the vast and complex alphabet soup of molecular interactions within cells, a relatively few biological pathways will turn out to be most important for many different diseases, Struhl suggested.
In experiments led by postdoctoral fellows Heather Hirsch, Ph.D ., and Dimitrios Iliopoulos, Ph.D ., the combination of metformin and the cancer drug doxorubicin killed human cancer stem cells and non-stem cancer cells in culture. The researchers used four genetically distinct breast cancer cell lines.
In mice, pretreatment with metformin prevented the otherwise dramatic ability of human breast cancer stem cells to form tumors. In other mice where tumors took hold for 10 days, the combination therapy also reduced tumor mass more quickly and prevented relapse for longer than doxorubicin alone. In the two months between the end of treatment and the end of the experiment, tumors regrew in the mice treated with chemotherapy alone, but not in those who received both drugs. Metformin was ineffective in treating tumors when used alone.
"This is an exciting study" said Jennifer Ligibel, M.D ., a medical oncologist at the Dana-Farber Cancer Institute and a Harvard Medical School instructor in medicine. Ligibel and colleagues at the National Cancer Institute of Canada Clinical Trials Group are developing a large-scale phase II trial and will study its metformin’s impact on recurrence in women treated for early stage breast cancer.
"There is a lot of interest in studying metformin in breast cancer, but so far we do not have direct evidence that metformin will improve outcomes in patients" said Ligibel, who was not involved in the current study "That’s what this trial is for"
So far, observational studies have suggested a lower risk of cancers, including breast cancer, and better response to chemotherapy in patients with diabetes who are treated with metformin, she said. Results of basic science studies have also suggested plausible biological mechanisms. The study from the Struhl lab suggests a potential new pathway through which metformin could have an effect on breast cancer cells, according to Ligibel.
In their search for compounds that selectively destroy cancer stem cells, researchers hope to improve cancer outcomes. But the story is never as simple in human cancers, according to Kornelia Polyak, M.D ., Ph.D ., a breast cancer researcher at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School.
Cancer stem cells are a shifty target, said Polyak, who was not involved in the current study. For example, any cancer cell can acquire the properties of a cancer stem cell, and cancer stem cells can change into non-stem cancer cells, which can be just as deadly. Clinical trials in people are needed to test these ideas, according to Polyak.
The study by Struhl and colleagues is an offshoot of a larger project in his lab to systematically track how gene activity changes when cells transform into cancer. These changes were remarkably similar to gene dynamics in diabetes and other inflammatory conditions.
The researchers reasoned that if a common genetic pathway underlies different diseases, drugs that work against one disease might work against another. In a screen, the most effective drug inhibiting the transformation of cells into cancer was metformin, which led to the experiments in this study. They were further encouraged by the low dose of metformin needed for the effect in the laboratory, compared to the amount needed for analogous molecular experiments in basic diabetes research. The relative dosage for treating or preventing cancer is unknown and untested in people.
Struhl and Harvard Medical School have applied for a patent for a combined therapy of metformin and a lower dose of chemotherapy, which is being tested in animals. The National Institutes of Health and the American Cancer Society funded this research.
News Briefing: The American Association for Cancer Research will host a news briefing about the results of this study, which is published online first in Cancer Research.
Date: Monday, Sept. 14, 2009
Time: 10:00 a.m. ET
Panelists:
Moderator - Frank Rauscher, III, Ph.D.
Editor in Chief, Cancer Research
Professor, Gene Expression and Regulation Program
The Wistar Institute
Kevin Struhl, Ph.D.
David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
George Prendergast, Ph.D.
President, CEO and Professor
Lankenau Institute for Medical Research
Jennifer Ligibel, M.D.
Medical Oncologist
Dana-Farber Cancer Institute
FDA Questions Denosumab Safety in Advisory Meeting Documents
By John Gever, Senior Editor, MedPage Today
Published: August 11, 2009
FDA staff has expressed concerns that denosumab, the investigational biologic drug for osteoporosis, may increase risk of serious infections through its activity against an important immune system modulator.
The agency believes the drug -- provisionally trade-named Prolia -- could delay fracture healing as well. Some evidence suggests it could also promote tumor development and progression.
The concerns were revealed in briefing documents released in advance of a Thursday meeting of the agency's Advisory Committee for Reproductive Health Drugs, which will consider whether to recommend denosumab for approval.
Denosumab is a monoclonal antibody to RANKL, the receptor activator of nuclear factor-?B ligand. The molecule appears to help drive osteoclast development and activation, as well as playing a vital role in the body's defenses against infection.
If NF-?B is the immune system's "master switch," as it has been called -- controlling B- and T-cell differentiation and dendritic cell development -- then RANKL is the finger that flips the switch.
The drug's manufacturer, Amgen, filed last December for FDA approval of denosumab for preventing and treating osteoporosis in postmenopausal women, in women undergoing hormone ablation for breast cancer, and in men on androgen-deprivation therapy for prostate cancer.
Just this week, two of the registration trials for denosumab were published by the New England Journal of Medicine as early online releases. Those randomized, placebo-controlled studies showed that the drug was as effective as the best bisphosphonate drugs for osteoporosis.
The studies included more than 7,800 postmenopausal women with osteoporosis and close to 1,500 men with prostate cancer.
They also reported no indications of increased rates of serious infections, cancers, or most other serious adverse events, except for an increased incidence of eczema. (See Denosumab a Winner in Phase III Osteoporosis Trials)
The drug also boasts an extremely convenient dosing regimen -- subcutaneous injection every six months. Many clinicians believe this is a big advantage for denosumab, considering that compliance with daily oral medications for osteoporosis is notoriously poor.
But the drug's risk profile, especially with regard to infections and cancers in women being treated for postmenopausal osteoporosis, appears to be the FDA's chief concern going into the advisory committee meeting.
After pooling data from the clinical studies in postmenopausal osteoporosis submitted by Amgen (including phase I and II trials), agency staff found hints of potential problems.
"Overall, subjects in the denosumab group had a slightly increased incidence of serious infections," according to the briefing document. "There were more serious infections of the skin, ear, abdominal system and urinary tract. Also, endocarditis, infected arthritis and skin ulcers occurred more commonly in denosumab subjects. There were three denosumab subjects in phase I studies who developed pneumonia requiring hospitalization following a single dose of denosumab."
The document also noted that while Amgen did not perform carcinogenicity studies in animals because denosumab is not active in normal mice or rats, the clinical data showed a modest increase in certain malignancies in the human subjects.
"Three subjects receiving a high dose of denosumab in [a] dose-finding study died of a new malignancy," the staff review found. Those individuals received 100-mg doses, whereas 60 mg was used in the phase III studies and would likely be the recommended dose upon approval.
Pooled data from all the postmenopausal osteoporosis trials suggested "a slightly increased incidence" of breast, pancreatic, gastrointestinal, and reproductive-tract tumors.
Twice as many women discontinued denosumab versus placebo because of breast cancer, the reviewers noted -- 0.5% (20 cases) of patients receiving denosumab versus 0.3% (10 cases) of the placebo group.
Certain data also indicated that denosumab may produce unhealthy changes in bone structure, the review found.
According to the briefing document, both osteoclasts and osteoblasts were suppressed relative to patients taking placebo and alendronate. Markers of bone dynamics such as activation frequency, bone formation rates, and mineralizing surface were also much lower in denosumab-treated patients.
"This raises a concern that with long term use, suppression of bone remodeling may lead to complications such as delayed fracture healing, osteonecrosis of the jaw, or atypical fracture," the document said.
Neither of the two New England Journal of Medicine reports this week, however, gave any indication of clinical bone problems associated with denosumab. Authors of those studies said they found no signs of delayed bone healing after fracture and there were no cases of jaw osteonecrosis, a rare but frightening side effect of bisphosphonate drugs.
The FDA document confirmed that no actual cases of jaw osteonecrosis were seen in any of the osteoporosis or hormone ablation trials.
But one case was reported in another trial sponsored by Amgen in patients with multiple myeloma and metastatic cancer.
Also, the clinical data alleviated concerns about possible adverse cardiovascular events, such as promotion of atherosclerosis, that were hypothesized on the basis of its anti-RANKL mechanism.
And, deaths were no more frequent in denosumab groups versus placebo in the trials.
In light of the safety worries that still remain with the drug, the advisory committee will be asked to comment on whether a risk evaluation and mitigation strategy should be required as a condition of denosumab's approval.
The agency is not bound to follow its advisory committee's recommendations, but it usually does.
Extreme Diet and Breast Cancer Risk
UK researchers observing a small group of women who followed an extreme 900 calorie a day diet found they had reduced expression of a cancer growth gene and changes in blood biomarkers for breast cancer. If these findings are confirmed in larger trials, the researchers hope they will help experts recommend specific diet changes to women at higher risk of breast cancer so they can reduce their likelihood of developing the disease.
The study was conducted by Professor Anthony Howell, Director of the Breakthrough Breast Cancer Research Unit at The University of Manchester, and his team, and was published online on 1 August in the journal Cancer Prevention Research.
Previous studies have already shown that calorie restriction, more formally termed Dietary Energy Restriction (DER), reduces the risk of spontaneous breast cancer in rats and mice, and in women who follow DER before the menopause it seems to reduce the risk of getting breast cancer after the menopause.
However, what is missing from the science is reliable markers of DER so that robust DER regimens for preventing breast cancer can be designed. So Howell and colleagues set out to investigate some DER biomarkers in breast and fat tissue and blood (serum).
For the study they recruited 19 women aged between 35 and 45 who were either overweight or obese and assessed to be at moderate risk of developing breast cancer due to family history (their lifetime risk ranged from 1 in 6 to 1 in 3).
The women were randomly assigned either to follow a DER regimen (10 participants) or continue a normal eating pattern (9 participants) of about 2,000 calories a day for one menstrual cycle.
Before and after the trial, the women underwent biopsies of breast and belly fat tissue and also gave blood and urine samples.
To look at genetic changes, Howell and colleagues extracted RNA from whole tissues and breast epithelium. To look for biomarkers, the blood and urine sample were used to generate metabolic profiles.
The results showed that:
• Not surprisingly, DER was linked to significant reductions in weight.
•
• DER was also linked to changes in serum biomarkers of breast cancer risk, including insulin, leptin (a hormonal biomarker for body fat), total and low-density ("bad") lipoprotein cholesterol, and triglycerides (high levels of these are often linked to higher risk of a range of diseases).
•
• In both breast tissue, belly tissue, and some isolated breast epithelial cells, there was evidence that genes involved in key metabolic pathways for fats and other substances (glycolytic and lipid pathways) were less active ("significantly down-regulated").
•
• This included a reduction in the expression of Stearoyl-CoA desaturase (SCD), a gene linked to cancer growth. This is the first time this has been observed in breast tissue.
Howell and colleagues concluded that:
"Reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents."
Howell told the media that he and his team wanted to thank the women who took part in the trial:
"The women who took part in this study made a major commitment to help us carry out this vital research."
"They enabled us to look for the first time at changes that occur within the breast tissue that may make cancer growth less likely. These results will now need to be tested in larger groups of women over longer periods of time," he added.
Dr Alexis Willett, Head of Policy at the UK charity Breakthrough Breast Cancer, said:
"We already know that the more weight a woman gains over the course of her adult life, the higher her risk of developing breast cancer will be after she has gone through the menopause. However, it is important to find out more about how lifestyle changes like losing weight can affect breast cancer risk."
"We wouldn't advise women to follow a diet of this kind as those who took part were closely monitored by a specialist dietician. We recommend that women maintain a healthy weight to reduce their breast cancer risk," added Willett.
Salinomycin Attacks Stem Cells in Breast Cancer
In tests in mice, salinomycin killed breast cancer stem cells far more effectively than some existing drugs, and slowed tumour growth.
The drug, a farm antibiotic, has yet to be tested in humans, the journal Cell reports.
But UK experts warned a human version could be some years away.
The reasons why, even following powerful chemotherapy, some cancers can grow back, are not fully understood.
Many scientists believe a key role lies with stem cells, which can be resistant to conventional chemotherapy, remaining to 'seed' new tumours and drive their growth.
The drug's potential was identified by researchers at the Massachusetts Institute of Technology, who tested 16,000 existing chemical compounds against breast cancer stem cells in the laboratory.
Those which performed the best were then tried in mice, and compared to existing drugs such as paclitaxel.
Salinomycin appeared to be 100 times better at killing the cells in a test tube, and treated cells were much less likely to start new tumours when injected into mice.
When given to mice with tumours, the growth of the cancer slowed.
However, the researchers stressed that it was too early to know if similar successes could be achieved in human cancer patients.
"Many therapies kill the bulk of a tumour only to see it regrow," said Professor Eric Lander, from MIT."This raises the prospect of new kinds of anti-cancer therapies."
'Very early research'
Dr John Stingl, group leader in mammary stem cell biology at Cancer Research UK's Cambridge Research Institute, said: "This is one of the biggest advances we have seen this year in this area of research. These scientists have demonstrated that it's possible to selectively target the rare cancer stem cells that drive tumour growth.
"This research also introduces a completely new way of identifying cancer drugs. The challenge for the future is to bring this class of drugs to the clinic and to identify the patients that are likely to respond to them."
Dr Alexis Willett, head of policy at Breakthrough Breast Cancer, added: "There is evidence that stem cells may enable breast cancers to form and grow.
"This research provides a clue as how to identify these cells and how they might be targeted and destroyed. "It's important to remember that this is very early research and it will be some time before it is clear whether this leads to an effective breast cancer treatment."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/8201376.stm
"Biomarkers of Dietary Energy Restriction in Women at Increased Risk of Breast Cancer."
Ong, Kai Ren, Sims, Andrew H., Harvie, Michelle, Chapman, Mary, Dunn, Warwick B., Broadhurst, David, Goodacre, Royston, Wilson, Mary, Thomas, Nicola, Clarke, Robert B., Howell, Anthony.
Cancer Prev Res 2009 2: 720-731.
Published online, August 1, 2009.
DOI: 10.1158/1940-6207.CAPR-09-0008
Sources: Manchester University.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Ovary Removal Linked to Increased Lung Cancer Risk
New York Times
By RONI CARYN RABIN
Women who undergo hysterectomies often have both ovaries removed along with the uterus in order to prevent ovarian cancer. But a new study suggests ovary removal may increase the risk of another seemingly unrelated ailment, lung cancer.
University of Montreal scientists stumbled onto the connection while investigating the relationship between lung cancer and hormones in women. They found no relationship between hormonal factors like menstruation patterns, child-bearing or breast-feeding histories and the risk of lung cancer. The researchers did, however, discover that women whose menopause had been induced medically were at 1.92 times greater risk of developing lung cancer than women who had experienced natural menopause.
“We were surprised — we had no prior expectation of this finding,” said Anita Koushik, a researcher at the University of Montreal’s Department of Social and Preventive Medicine and the first author of the study, published online in May in The International Journal of Cancer. “Aside from the fact that smoking increases your risk of lung cancer, the results of this study suggest that having a non-natural menopause contributes to an almost doubling of the risk.” She noted, though, that the findings could have occurred by chance.
The vast majority of women who had experienced a non-natural menopause had had both ovaries surgically removed, she added.
While smoking is the leading cause of lung cancer, other factors may play a role in enhancing the impact of the carcinogens in tobacco, Dr. Koushik said. In women, these factors could be hormonal. Both normal and cancerous lung tissue express estrogen receptors and may be influenced by levels of the hormone in the body, Dr. Koushik said. The patterns of expression are different in men and in women.
Medically induced menopause usually occurs at a younger age than natural menopause. Surgical menopause results in a sudden drop in estrogen levels, compared with the more gradual decline in hormone levels that occurs with natural menopause. Dr. Koushik suggested the increased lung cancer risk may be linked to the impact of plummeting hormone levels.
In the study, the scientists examined data on 422 women diagnosed with lung cancer in the greater Montreal area in 1996 and 1997 and compared them with 577 randomly selected control subjects. The women were asked about a variety of hormone-related factors, including when they got their first periods, how many children they had, whether they breast-fed their children and whether they had gone through menopause. The researchers also gathered detailed information about smoking, occupational history, education and family income.
The report is not the first to link ovary removal with an increased risk of lung cancer. A recent analysis of data from the Nurses’ Health Study, published in the journal Obstetrics and Gynecology in May, reported that women who had had hysterectomies but kept their ovaries lived longer than women who had had the procedure but whose ovaries were removed.
While those who had their ovaries removed were less likely to develop breast cancer and virtually eliminated their risk of ovarian cancer, they were more prone to heart disease and were at greater risk for other kinds of cancer, including a doubling of the risk for lung cancer among those women who never used hormone therapy.
(See 2009 SABCS Report on how Aromatase Inhibitors reduce lung cancer risk)
Blood Pressure Drug Blocks Newly Found Breast Cancer Gene
Blood Pressure Drug Losartan Shrinks Cancer Tumors by 30% in Study
By Gina Shaw
WebMD Health News
Reviewed by Louise Chang, MD
June 1, 2009 -- Researchers at the University of Michigan have identified a gene that may be involved in as many as one in five breast cancers. And the gene could be blocked by a common blood pressure drug.
The gene, AGTR1, caused normal breast cells to act like highly invasive cancer cells, both in the laboratory and in mice. When the mice were then treated with an FDA-approved blood pressure drug, losartan, tumors that overexpressed AGTR1 shrunk by 30% within eight weeks.
The Hunt for Breast Cancer Genes
The researchers identified AGTR1 by using gene expression profiling data to compare thousands of genes that might be linked to breast cancer. AGTR1 was overexpressed (or overly productive of its gene product) in 10% to 20% of all breast cancers -- second only to HER2, which is found in 25% to 30% of all breast cancers and responds well to the drug Herceptin.
“HER2 ... makes breast cells cancer-like. That’s very similar to what we found with AGTR1,” says Daniel Rhodes, PhD, a research investigator in the Michigan Center for Translational Pathology and the lead author of the study, which appears in the June 1 edition of Proceedings of the National Academy of Sciences. Rhodes is also the founder and CEO of a cancer genomics company, Compendia Biosciences.
Breast cancer researchers have been looking for other targets similar to HER2 in order to develop more targeted treatments for women whose breast cancers are not HER2-positive and therefore do not respond to Herecptin.
Blood Pressure Drugs for Breast Cancer
Because AGTR1 is involved in the constriction of blood vessels, its activity is blocked by a class of drugs called angiotensin receptor blockers, which include losartan, the drug tested in this study. “This is particularly exciting, because losartan is such a safe and widely prescribed therapy,” Rhodes says. “This makes it much easier to do a clinical trial.”
If losartan really does block the cancer-promoting activity of AGTR1, why hasn’t anyone identified a lower rate of breast cancer among women taking the drug for high blood pressure?
“One would expect epidemiologic studies to show a reduction in BC [breast cancer] risk in people taking this drug,” says Clifford Hudis, MD, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York. “I don’t remember ever seeing hypertension and treatment for hypertension as indicators of lower breast cancer risk. We have lots of patients who get treated for breast cancer and take anti-hypertensives, so you would expect to see that pop out as an indicator of good outcomes.”
But not all high blood pressure drugs specifically block the AGTR1 receptor. “We think that true blockers to the AGTR1 protein would have the strongest effect, and these drugs, like losartan, are generally used as second-line therapies for hypertension,” Rhodes tells WebMD. "If only a few women in 100 are being treated with angiotensin receptor blockers, and only 10% to 20% of all breast cancers are AGTR1-positive, you’d need thousands of patients to see an effect.”
Developing a Test for AGTR1-Positive Tumors
But if there were a study in which losartan were given only to women with breast cancers linked to overexpression of AGTR1, it would be much easier to detect an effect. Before such a trial can be set up, however, scientists must first develop a way to easily detect AGTR1 overexpression.
Once that test is available -- something that should take only a few months, says Rhodes -- a clinical trial should be easier than usual to set up because of the availability of an existing, approved therapy whose side effects are known. “No trial is specifically planned yet, but we are talking with our clinical colleagues about it and there is a great deal of interest,” he says.
“If the data can be confirmed, it’s not a big stretch to imagine setting up a randomized study relatively easily,” Hudis says. “I definitely think this should be investigated further, although as always when we don’t yet have data in humans, you have to be careful and not jump to conclusions.”
The University of Michigan has filed a patent on AGTR1 and is seeking commercial partners.
New report states that breast ultra sounds are 100% accurate. Read on to see how misleading this is.
A new report has been released today to tell us all that breast ultrasounds pick up tumors 100% of the time in women under 40.
Really?
My tumor, which was found when I was in my 30s, was picked up on mammogram and when the docs did a follow-up ultrasound it was not there. The radiologist said that since it was not picked up on both, I should "watch and wait" for six months.... Fortunately I have a gyn who hates cancer as much as I do and he insisted on an immediate biopsy. That resulted in finding a grade 3, highly aggressive Triple Negative Breast Cancer next to my chest wall. If I had followed the three most dangerous words in the English language, "watch and wait" my TN tumor would have made a nice, comfy home for itself in the chest wall and the vascular and lymphatic system. Would I still be here? I don't know- Ferne isn't... and she was told to wait.
Here is the article- tell your friends to not take this as gospel because it could be deadly. The TRUTH IS: Women under 40 need better screening. It is NOT just replacing mammography with ultrasounds. If they really gave a damn about us they would find a way to get EVERYONE Breast MRIs which can find tumors as small as 7mms. But who is going to pay for that? We have research into erectile dysfunction to fund.... the Space Shuttle to launch to change the spark plugs on the International Space Station.... Think about it.
CHICAGO (Reuters) - Breast ultrasounds found 100 percent of suspicious cancers in women under 40 who found lumps or other suspicious areas of the breast, offering a cheaper, less-invasive alternative to surgery or biopsies, U.S. researchers said on Wednesday.
They said targeted ultrasound -- which examines just the area of the breast where a lump is identified -- should become the standard of care for women under 40.
The findings may address some of the concerns raised by a federal advisory panel about breast exams done by women or doctors to investigate lumps or hot spots in the breast, which most often turn out to be harmless.
In a controversial set of recommendations issued last month, the U.S. Preventive Services Task Force recommended that women not be taught to perform self breast exams because they often result in worry and expense for tests, biopsies and unnecessary surgery.
"That concerns us because while breast cancer in young women is rare, it absolutely does occur. Often, those cancers are only diagnosed because the woman noticed the lump in her breast or her doctor noticed a lump in her breast," said Dr. Constance Lehman of the University of Washington and director of imaging at the Seattle Cancer Care Alliance, who presented her findings at the Radiological Society of America meeting in Chicago.
"There are harms that follow after a woman does a self breast exam -- unnecessary surgeries, unnecessary biopsies. To that point, what we're saying is if you use imaging appropriately you can avoid those harms," Lehman said in a telephone interview.
Lehman did two studies testing the effectiveness of ultrasound to distinguish between potentially cancerous lumps and harmless masses in younger women.
In one, they studied more than 1,100 ultrasound exams of women under age 30. In the second, they studied 1,500 exams in women aged 30 to 39.
In both studies, ultrasound correctly identified the cancers and all of the benign breast changes. The only cancer not found was in a region of the breast that was not identified as an area of concern. Instead, it was identified by a full breast mammogram.
"Less than 3 percent of the patients that presented in this way had cancer. But it's important for us to find those patients that did have cancer," Lehman said.
"We had 26 women whose cancers were diagnosed because they brought the lump to the attention of their doctor, or their doctor brought the lump to the attention of the breast imaging specialist," she said.
Lehman said in the United States there is no standard way of treating women under age 40 who find a lump in their breast.
"Some of them go to the operating room to have the lump removed. Others have it followed. Others have a needle biopsy and we wanted to bring some clarity to this treatment," she said.
She said ultrasound is a quick and easy test that uses sound waves to create an image of the breast. It typically costs $100 to $200 per exam.
Lehman said using ultrasound could help balance some of the harms of overtreatment with the benefits of self breast exams in women under age 40, who are too young for routine mammogram screening even under the American Cancer Society guidelines.
The task force also recommended against routine mammogram screening for women in their 40s for many of the same reasons, a change the American Cancer Society and many other breast cancer experts reject.
On Judah Folkman and Avastin
The very miracle that gives us life can also take it away. This is what Dr. Judah Folkman discovered when he realized the mechanism of angiogenesis. Angiogenesis: the creation of a new blood supply from cells within the body. The most beautiful of angiogenesis is a fetus. The most deadly is found in cancer.
Two polar opposites, that which gives life and that which takes it away, are both developed through angiogenesis.
When Dr. Folkman made his discovery, over two decades ago, the world thought the key to unlocking the door that stops cancer had been found. However, it was not so easy. Creating an anti-angiogenesis drug proved difficult if not impossible. Until Avastin (Bevacizumab) hit the oncology world. It showed in clinical trials that it stops cancer cells from creating their own blood supply, thus stopping cancer from growing.
It was paired with other chemotherapies and there were some very good outcomes along with some deadly side effects, for some. However, it did work on women who had advanced breast cancer. It also showed promise in the treatment of early stage disease. I personally know women who benefited from this drug. It represented the future of cancer care. Until now.
This week, the FDA is considering pulling it from the market because studies show "not enough benefit compared to the risk when paired with current chemotherapies." Women who are currently benefiting from this drug will lose their insurance coverage for Avastin if the FDA succeeds in pulling this drug.
Avastin is a powerful weapon in the arsenal against breast cancer. If the FDA does not feel it works well with current, well established chemotherapies, they should have a warning for practitioners and patients alike. But they must not close the door for its use for future drugs that it may work extremely well with. One example is the new hope that is being found in Parp Inhibitors for triple negative disease. There has not been sufficient testing of Parp i, nor has there been combination trials of Avastin with these future drugs to completely rule out this hope for women who are desperate for a therapy that will extend their lives.
Pull Avastin from the market? The FDA should ask the women whose metastatic disease is now stable because of it before they close yet another door on survival. If Dr. Folkman were still alive today, he would most likely agree.
FDA May Pull Avastin From Market
Molly Peterson, BLOOMBERG News
Roche Holding AG’s top-seller Avastin may shed $1 billion in annual revenue if U.S. regulators follow a panel recommendation to revoke approval of the drug for use in breast cancer.
Scientific advisers to the Food and Drug Administration voted 12-1 yesterday to rescind Avastin’s clearance in breast cancer after finding the drug paired with chemotherapies didn’t work better than other medicines alone. The agency usually follows panels’ advice, though it isn’t required to do so.
Roche, Europe’s largest drugmaker, won FDA approval of Avastin for breast cancer in 2008 under an accelerated review that required the company to conduct trials proving the drug, with $5.97 billion in sales last year, slows progression of the disease. Tests failed to meet this goal, the FDA panel found. Withdrawal of U.S. approval could trim as much as $1 billion from annual sales by 2015, said Sanford C. Bernstein & Co. analyst Tim Anderson, in a report yesterday after the vote.
“Given the overwhelming majority against Avastin, we think there is a good chance the FDA will follow the committee’s advice,” Anderson said. He projected worldwide Avastin sales of about $6.5 billion this year, including approximately $1.2 billion from breast cancer. Eliminating U.S. breast cancer sales may cut Roche’s earnings a share by about 5 percent, he said.
No Expanded Use
Panelists also rejected Roche’s application to expand use of Avastin in breast cancer for pairings with more varieties of chemotherapy. Wider use from that approval could have pushed global breast-cancer revenue for Avastin to about $3 billion a year, said Martin Voegtli, an analyst with Kepler Capital Markets in Zurich, in a telephone interview yesterday before the panel vote.
“We are disappointed by the committee’s recommendation and believe Avastin should continue to be an option,” Sandra Horning, head of clinical development hematology/oncology at Roche said in an e-mailed statement today. “We will continue to discuss the data from the more than 2,400 women who participated in three phase III studies with the FDA.”
Roche, based in Basel, Switzerland, fell 6 Swiss francs, or 4.2 percent, to 137 francs at the 5:30 p.m. close of trading in Zurich. The stock declined 4.2 percent, the most in more than a year, July 16 after a FDA report concluded Avastin didn’t slow breast tumors in new studies as much as in earlier tests used to win approval.
“It is clear that the FDA do not believe Avastin adds a clinically meaningful benefit to patients,” said Dominic Valder, a London-based analyst with Evolution Securities, in a July 19 research report.
Sept. 17 Decision
“Today’s advisory committee vote does not change the current availability of Avastin for women with advanced breast cancer,” Charlotte Arnold, a spokeswoman for Roche’s South San Francisco, California-based Genentech unit, said yesterday in an e-mailed statement. The FDA will make a final decision by Sept. 17, she said.
Avastin is the first medicine to fight cancer by blocking the growth of blood vessels that feed tumors, a process called angiogenesis. It targets a chemical signal known as vascular endothelial growth factor, or VEGF. The treatment, also approved for brain, lung and colon tumors, costs about $50,000 a year. Avastin was developed by the company’s Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.
Most Common Malignancy
Breast cancer is the most common malignancy in females and strikes about 1 million women a year globally, according to the Geneva-based World Health Organization. Avastin is approved for about three quarters of women whose breast cancer has been recently diagnosed as having spread to other organs. It doesn’t include women who have a mutation to the HER2 protein, a known risk factor. Patients with HER2 mutations are eligible for another Roche drug, Herceptin.
The FDA’s 2008 clearance of Avastin for breast cancer overruled an advisory panel that concluded the benefit of slowing the spread of tumors wasn’t worth the risk of side effects including high blood pressure and death.
Approval was based on a clinical trial, called E2100, which showed Avastin slowed the spread of breast cancer by an additional 5.5 months when paired with paclitaxel chemotherapy, compared with the other drug alone, the FDA said in its report.
One trial completed since then, called Avado, showed that a high dose of Avastin paired with docetaxel chemotherapy extended the time patients lived without their disease worsening by 0.9 months, compared with treatment with chemotherapy alone, the FDA report said. A lower dose of Avastin gave patients 0.8 months.
Extended Life
A second trial finished after approval, called Ribbon-1, found Avastin combined with taxane or anthracycline-based chemotherapies stalled tumor growth by 1.2 months, compared with treatment with chemotherapy alone, the agency said in its review. Patients who got Avastin combined with Xeloda lived 2.9 months longer without their disease progressing, compared with chemotherapy alone.
“We have a far more comprehensive picture here of the role of Avastin than we had in 2008,” said Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, told the panel before yesterday’s vote.
Drugs that win conditional clearance through the FDA’s accelerated-approval program can later be pulled from the market if subsequent data fails to show that a treatment increases long-term survival or slows progression of the disease while improving quality of life.
‘Overwhelming Majority’
While Avastin is expensive and doesn’t work as well as early trials suggested, the “overwhelming majority” of breast cancer specialists think the drug has a use in certain patients, Jack Scannell, a Bernstein analyst in London, said in a July 15 research note.
Breast-cancer patients may lose insurance coverage for Avastin if the FDA revokes approval of the treatment, said Francisco Esteva, a professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.
“Even if we wanted to use it, patients would have to consider that it’s a very expensive therapy,” Esteva said July 15 in a telephone interview. “Without insurance support, I don’t think patients would be able to take it.”
WHAT IF...?
We have written several articles, blog posts and shared too many personal stories to take this anymore. Women are not getting early screening for breast cancer and that means their cancers are being found too late. They are found spread to lymph nodes and distant organs - found too late to treat - too late to do anything that could be prevented.
We do NOT have a cure yet. Until then, it is up to US, to take the pledge and save the lives of women who do not even know they have breast cancer: Because early detection is our ONLY DEFENSE.
Are you ready? Take the Before Forty Initiative Pledge!
Mammogram uproar as pols, doctors reject guidelines
Originally published: July 11, 2010 6:32 PM Updated: July 11, 2010 9:42 PM By DELTHIA RICKS
Eight months ago, a federal advisory panel triggered an uproar by saying most women needed fewer mammograms and should begin them at a later age. Today, the confusion over those guidelines has intensified as physicians and lawmakers demand they be withdrawn.
The recommendations suggested women without risk factors for breast cancer could wait until 50 to start annual screening. Within a day of their release, Health and Human Services Secretary Kathleen Sebelius issued a statement saying the guidelines didn't represent government policy, and advised women to "do what you've always done."
But the guidelines from the U.S. Preventive Services Task Force, a panel of outside experts chosen by HHS, are still posted on an official government website run by Health and Human Services although they have been modified slightly to say women between 40 and 49 who want a mammogram should get one if their doctor recommends it.
Still, the furor over the guidelines will not go away.
Sen. David Vitter (R-La.) wrote to Sebelius in May saying passage of the Patient Protection and Affordable Care Act in December required that the government withdraw the guidelines.
Vitter said the bill, passed by a bipartisan vote, called on HHS to remove the recommendations from its website and "cease all promotion of the November 2009 recommendations related to breast cancer screening and mammography"
In his letter, he wrote: "The fact that these recommendations are still being presented to the general public as 'current' is only serving to further confuse women on this critical issue. The recommendations were ill-conceived from the start. . . . They represent a step backward in our fight against a horrible disease."
Vitter spokesman Joel DiGrado said they have yet to receive a reply from Sebelius. "The senator's office has not heard anything back from HHS. This is not all that untypical for an agency. Their responses to formal letters can take quite some time."
Newsday made several attempts to get HHS to address the status of the guidelines - whether the agency still endorses them now that they've been edited, or whether they will be withdrawn, as some lawmakers are seeking. The agency did not provide answers to the questions and no one from HHS would address whether scrapping the guidelines is seriously under discussion.
Dr. Christine Hodyl, director of breast surgery at South Nassau Communities Hospital in Oceanside, said she never took the guidelines seriously - they're unrealistic for Long Island.
"This week alone," she said recently, "I operated on two women. One was 37 and the other was 41. Here on Long Island, the breast cancer rate is so high I tell women to get their baseline [first mammogram] at 35 to 40. If these [two] women had waited until 50, the cancer would have metastasized."
Another critic, Dr. Brian O'Hea, director of the Carol M. Baldwin Breast Care Center at Stony Brook Medical Center, said he never stopped recommending routine screening at age 40. "We're still in line with the American Cancer Society and have not changed a bit," O'Hea said.
Last month, a Harvard mammography expert charged that the guidelines are based on faulty science and should be retracted.
None of the task force members were experts in breast cancer or mammography.
Health care insurers, such as Empire BlueCross Blue-Shield and Vytra, say they are sticking with the cancer society's recommendations.
http://www.newsday.com/news/health/mammogram-uproar-as-pols-doctors-reject-guidelines-1.2096878
There is now proof that the US Task Force has done damage. This group of people announced in the fall that women under 50 years of age do not need mammograms. The No Surrender Breast Cancer Foundation is vehemently against this decision and has made our opinion known.
Our Before Forty Initiative is working hard to get the word out to all women that Early Detection is your BEST defense. If you want the highest chance of beating cancer: find it while it is still small. That is why we are educating women about the importance of baseline screenings BEFORE the age of Forty and follow-up care that involves not only mammography, but ultra sound and breast MRI.
We need your help to help us save the lives of women.
Please see our BEFORE FORTY INITIATIVE HERE.
Please DONATE to our foundation to help us. We need funding.
Read today's news, and you will find more proof why it is our duty to protect the women who come after us.
Mammogram screening down 13 percent since 'flawed' recommendations
By Aimee Heckel Camera Staff Writer
Posted: 06/23/2010 09:14:36 AM MDT
Read more: Mammogram screening down 13 percent since 'flawed' recommendations - Boulder Daily Camera http://www.dailycamera.com/lifestyles/ci_15351198#ixzz0ri8xRW5J
DailyCamera.com
Terry Stiven, of Lafayette, almost didn't get the test.
She had no family history of breast cancer. She'd had mammograms in the past, and she had no signs of cancer.
Then, this fall, the United States Preventative Service Task Force released new recommendations: Women between 40 and 49 years old don't need mammograms. The benefits of testing don't outweigh the risks, the task force said.
Now, it seemed there was no reason to get the 10-minute, slightly uncomfortable screening. In February, Stiven, 46, went ahead and got tested anyway, expecting nothing.
She had cancer.
Not invasive breast cancer, though. Doctors removed the lump, and she had four weeks of radiation. The experience was frightening, but not damaging.
Today -- just four months later -- Stiven is cancer-free, with extremely low chances of it returning. She still has both breasts, she runs triathlons and her life expectancy has not been shortened.
"If I'd waited four years, I don't know if I would have been alive," she says.
Stiven is one reason of many that local doctors have launched an aggressive campaign to counter the U.S. Preventative Task Force's advisory.
"Getting a mammogram is one of the most important things a woman can do to live a long, healthy life," says David Oppenheimer, the chief physician of the mammography department of the Boulder Community Hospital.
And he's not just talking about women older than 50.
One third of women diagnosed with breast cancer in Boulder County are between 40 and 49 years old, according to the Boulder Community Hospital. More than 40 percent are younger than 50 -- the task force's "arbitrary" age cut-off, Oppenheimer says.
Since the task force's recommendation, the hospital's imaging department reports a 13 percent decline in mammograms -- the majority among women in their 40s and 50s.
Nanna Bo Christensen, the Boulder Community Hospital's Breast Health Navigator, attributes this drop at least in part to the national recommendation.
Other women may be afraid they can't afford it -- even though it is illegal in Colorado for insurance companies not to cover screenings for women age 40 and older. The Women's Wellness Connection offers financial support for women who need it, too, says Christensen.
"Mammography saves lives," she says. "The key to survival is early detecting."
In fact, the younger the woman, the faster the breast cancer grows, doctors say, due to higher levels of estrogen, which feeds the cancer cells.
And if you find cancer before it spreads to the lymph nodes, Oppenheimer says, doctors have a 97 percent chance of curing it. Once it hits the lymphs, the cure rate plunges.
The number of women who die from breast cancer is down since 1990, and experts say that's primarily due to increases in the number of women being screened.
So why would a government panel recommend against something that statistics show helps save lives?
The task force looked at false-positive tests and the related anxiety, unnecessary biopsies and exposure to radiation.
Oppenheimer asserts data used for the recommendation was scientifically flawed, and that the task force left out several important studies to skew the numbers in favor of its recommendation. As to the radiation question, he says about 1 in 3 million mammograms actually causes cancer.
"However, we know that one in eight women are going to get breast cancer in their lives, so the advantages far outweigh the tiny risk," he says.
Mammograms detect cancer 90 percent of the time, the hospital says, making them the most effective screening tool.
A slew of organizations have since denounced the recommendation, including the National Cancer Institute, the American Cancer Society, the Susan G. Komen Breast Cancer Foundation, Avon Foundation, the Obama Administration, American College of Radiology, American Society of Breast Imaging, American College of Obstetricians and Gynecologists.
"Now we as physicians and a health care community have a huge job on our hands to re-educate the community," Oppenheimer says. "Once people stop getting tested, it's a huge effort to convince people to start again."
The U.S. task force also said women older than 50 only need to get a mammogram every two years instead of annually.
When Jill Kamon, of Boulder, heard that, she says she was horrified.
Kamon was diagnosed at age 51 with breast cancer. If she had followed the recommendations, she would have skipped the mammogram that found the small lump in the back of her breast. The cancer would have had a year to grow before her next mammogram. She couldn't feel it with a self-exam.
"To me, the mammogram and radiologist who read the mammogram completely saved my life. There is no question," says Kamon, who had a double mastectomy in the summer of 2007. The lump was only 6 millimeters big, but it was growing aggressively.
"I'd had a mammogram exactly one year earlier that was clear," she says. "That dot was not there."
By the numbers
13 percent -- Decrease in mammograms at the Boulder Community Hospital since the U.S.
Preventative Service Task Force recommendation in the fall. The majority of these women are in their 40s and 50s.
30 percent -- Decrease in breast cancer's death rate since 1990, nationally.
42 percent -- Of women diagnosed with breast cancer at the Boulder Community Hospital were younger than 50; 32 percent were in their 40s.
More than 30 percent -- Decreased death rate, due to mammography screenings for women in their 40s.
One in eight -- American women are affected by breast cancer.
97 percent -- Chance of curing breast cancer if it's caught before spreading to the lymph nodes.
About 1 in 3 million -- Chance of the radiation from a mammogram causing breast cancer.
Sources: Boulder Community Hospital, Susan G. Komen for the Cure.
Important information for Tamoxifen Users
OncologySTAT has released this very important discussion about CYP2D6 enzyme and tamoxifen. Be aware that there are drugs you may be taking that could render Tamoxifen powerless, leaving you vulnerable for breast cancer recurrence.
Dr. Matthew P. Goetz: Tamoxifen Metabolism, Endoxifen, and CYP2D6 Polymorphism
2010 Jun 15, Interview by L Scott Zoeller
Please go to THIS LINK for more information.
Get moving after breast cancer surgery...
See our post surgical exercises HERE
Exercise Preserves Freedom of Movement After Breast Cancer Surgery
Washington, June 16 (ANI): A study has found that exercise can help patients maintain shoulder movement and minimize loss of arm or shoulder function after breast cancer surgery.
The new Cochrane review found exercise programs needed to be created to help patients who have just had surgery, as most survivors develop pain, shoulder stiffness and arm swelling after treatment.
Physicians usually prescribe arm and shoulder exercises after surgery to prevent pain and stiffness in those areas on the side of the cancer, but the problems often persist for years.
"There has been some concern that too much aggressive movement soon after surgery might cause pain, delay healing, and increase the risk of arm swelling," said lead review author Margaret McNeely, an assistant professor of physical therapy at the University of Alberta and clinical researcher at the Cross Cancer Institute, in Canada.
McNeely's team examined 24 research studies comprising 2,132 women with a confirmed breast cancer diagnosis and who had undergone surgery such as a radical mastectomy, modified radical mastectomy, or a local wide excision or lumpectomy.
They had also all had surgery removing lymph nodes from the axilla, or armpit, to determine the extent of the cancer.
Specially designed programs included range-of-motion movements for the shoulders and stretching exercises.
The review showed that starting exercise early after surgery, within the first to third day, might result in better shoulder movement in the early weeks following surgery.
"However, starting exercise that soon after surgery may cause more wound drainage and require drains to remain in place longer than if exercise is delayed by about one week," McNeely said.
The Cochrane Collaboration, an international organization that evaluates medical research, published the review.
Fourteen studies compared the effect of structured exercise to usual care, in which women received an exercise pamphlet or no exercise instruction at all.
Of these, structured programs including physical therapy regimens in the early postoperative period led to a significant improvement in shoulder range of motion over the short and long term.
"Several persistent complications can greatly diminish a patient's quality of life," said Douglas Blayney, M.D., medical director at the University of Michigan's Comprehensive Cancer Center.
Blayney said that although current surgical treatment is attempting to move away from disturbing the axilla, more women, especially younger women, are choosing mastectomy over breast conserving surgery.
"Combined, these trends in primary treatment of breast cancer make this review highly relevant," said Blayney, who has no affiliation with the review.
Nevertheless, he noted that making suitable exercise programs widely available to breast cancer patients in a timely manner would be a challenge.
He said optimal breast cancer care now involves a team with a wide range of health specialists: surgeons, radiation oncologists, medical oncologists, reconstructive surgeons and others.
"This review demonstrates that early involvement of a new team member who manages exercise or physical therapy is also useful for the best outcome," he said.
"Implementation of modern primary treatment strategies - - including early intervention with suitable exercises - should reduce the incidence of these heartbreaking complications," Blayney added. (ANI)
Sequential seems superior...
Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast Cancer
N Engl J Med. 2010 Jun 3;362(22):2122-2124, SM Swain, JH Jeong, CE Geyer Jr, JP Costantino, ER Pajon, L Fehrenbacher, JN Atkins, J Polikoff, VG Vogel, JK Erban, P Rastogi, RB Livingston, EA Perez, EP Mamounas, SR Land, PA Ganz, N Wolmark
ABSTRACT
In this study that enrolled more than 5000 women with early-stage, node-positive, operable breast cancer, chemotherapy with sequential-ACT improved both DFS and OS when compared with four cycles of doxorubicin/docetaxel...
Background: Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.
Methods: We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.
Results: At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.
Conclusion: Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status.
Liver Mets? Consider Surgery
Liver Resection for Multimodal Treatment of Breast Cancer Metastases: Identification of Prognostic Factors
Ann Surg Oncol. 2010 Jun 1;171546-1554, K Hoffmann, C Franz, U Hinz, P Schirmacher, C Herfarth, M Eichbaum, MW Büchler, P Schemmer
In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.
STUDY IN CONTEXT
The role of liver resection (LR) is controversial as a component of multimodal therapy for hepatic metastases (HM) associated with breast cancer. Thus, a better understanding of the benefits and clinical outcomes of the surgical approach is needed, along with identification of the potential prognostic factors for long-term survival.
To this end, Hoffmann et al. retrospectively evaluated data that were prospectively collected for 41 patients with hepatic breast cancer metastases. All of these patients underwent exploratory laparotomy for LR. Of the 41 patients, 40 patients had primary tumor adenocarcinoma, and 1 patient had a mucinous carcinoma of the breast. Patients selected for hepatic resection were stable, having no more than five metastases and with extrahepatic metastases under remission. No vascular invasion was evident, and R0 resection was deemed possible. Karnofsky index was ≥80%.
The median time from treatment of the primary breast tumor to diagnosis of HM was 3.4 years (interquartile range [IQR], 1.2–8.0 years). Segment resections were performed in 19 patients (45%) and major hepatectomy was performed in 22 patients (right hemihepatectomy, 25%; left hemihepatectomy, 12%; extended right hemihepatectomy, 7%; extended left hemihepatectomy, 9%).
The primary outcome measure was overall survival from the date of LR. Secondary outcome parameters were disease-free survival, progression-free survival, and recurrence-free survival from the date of LR and overall survival from the date of primary breast tumor operation.
Median follow-up was 34 months after LR (IQR, 8–68 months). The estimated median survival was 58 months. The 3- and 5-year survival rates after LR were 68% and 48%, respectively, although they were 80% and 59%, respectively, from the time of diagnosis of HM, with an estimated median survival of 79 months. The 5-, 10-, and 15-year survival rates after treatment of the primary tumor were 84%, 76%, and 50%, respectively, with a median survival of 211 months. Incidence of HM earlier than 12 months after treatment of the primary tumor (5-year overall survival, 28%) was associated with a three-times-higher likelihood of mortality (hazard ratio, 3.8) compared with HM occurring later than 1 year after treatment of the primary tumor (5-year overall survival, 58%). R0 resection resulted in 3- and 5-year survival rates of 80% and 62%, respectively, while patients after R1/R2 resection had a median survival of 28 months after LR, with patients six times more likely to die compared with patients after R0 resection (hazard ratio, 6.3).
In the absence of extrahepatic metastases at the time of LR, the 3- and 5-year overall survival rates were 75% and 59%, respectively, compared with rates of 51% and 31%, respectively (P = 0.15), for patients who did have extrahepatic metastases.
Following R0/R1 resection, patients without extrahepatic disease at the time of LR (n = 26) had an estimated median disease-free survival of 34 months; the 3- and 5-year disease-free survival rates were 46% and 31%, respectively, with HM reducing the respective rates to 26% and 13%.
The median time to intrahepatic recurrence in patients without extrahepatic disease at the time of LR was 8.6 months; the 3- and 5-year intrahepatic recurrence-free survival rates were 71% and 62%, respectively.
The results of this study showed that, in patients with hepatic breast cancer metastases (without any type of peritoneal carcinomatosis and/or positive hilar lymph nodes), LR was safe and improved long-term survival. No perioperative deaths occurred during this study.
Check that label first...
Some sunscreens contain dangerous chemicals
June 4, 2010 3:10 PM
By MCCLATCHY-TRIBUNE
We all know it's important to use sunscreen. But it's also important to check the label for ingredients that are safe for you and the environment.
The Environmental Working Group, a nonprofit public health and environmental research and advocacy organization based in Washington, D.C., studied nearly 1,000 brand-name sunscreens in 2009. Three in five did not adequately protect skin from the sun or contained harmful chemicals.
One controversial sunscreen ingredient is oxybenzone. It absorbs ultraviolet light, but research shows it also can be absorbed through the skin. The Centers for Disease Control and Prevention released a study in 2008 showing that 97 percent of Americans it tested were contaminated with oxybenzone.
Oxybenzone is allowed in sunscreens, but recent research has linked it to allergies, hormone disruption and cell damage that can lead to skin cancer. It's bad for the environment, too. Researchers believe oxybenzone, once washed down the drain or off swimmers' bodies, contributes to the feminizing of certain species of male fish in our oceans, rivers and lakes.
So why is oxybenzone still considered "safe" in sunscreens? Unfortunately, the Federal Drug and Food Administration, which regulates sunscreen safety, has not updated mandatory sunscreen standards in more than 30 years.
What should you do? Look for a broad-spectrum sunscreen that offers protection from both UVA and UVB rays but does not contain oxybenzone.
Sunscreens containing zinc oxide or titanium oxide are recommended by the Environmental Working Group.
Emerging studies show that we are out of balance with too much Omega 6 verses the healthy Omega 3s. Extra virgin olive oil helps us regain that balance. Stay away from other fats and processed foods and you will not only feel the difference, but you will see it, too.
Breast Cancer Survivors Lose More Weight On Olive-Oil Enriched Diet
04 Jun 2010
Researchers from The Miriam Hospital have found that olive oil may offer another potential health benefit - it produces greater weight loss in breast cancer survivors compared to a more traditional low-fat diet.
The findings may be of significance to women with breast cancer, since excess weight at the time of diagnosis, or even moderate weight gain during cancer treatment, is associated with an increased risk of cancer recurrence, particularly in post-menopausal women.
In this pilot study, women followed two 1,500-calorie diets - a conventional low-fat diet recommended by the National Cancer Institute (NCI) and a plant-based olive oil diet similar to the Mediterranean diet. After eight weeks on each diet, participants selected one diet to follow for an additional six months of continued weight loss or weight management.
According to the findings, published in the June issue of the Journal of Women's Health, 80 percent of women who started with the plant-based olive oil diet lost more than 5 percent of their baseline weight, compared to 31 percent who started with the NCI diet. But researchers were most surprised to find that after trying both diets, most women chose to stick with the less conventional, higher fat olive oil diet, saying they found the food more appetizing, accessible and affordable.
Mary Flynn, PhD, RD, LDN, the study's lead author and a research dietitian at The Miriam Hospital, says many breast cancer patients don't realize there is a link between weight and cancer recurrence.
"That's why it was important for us to compare these two diets and determine which one the women not only enjoyed following, but also produced the best weight loss, because that's the diet they're more likely to stick with," says Flynn. "In this case, it was a diet enriched with extra virgin olive oil, which is a source of healthy fats, and includes foods associated with improving one's health, such as vegetables, beans and other plant products."
Extra virgin olive oil has been associated with decreasing breast cancer risk in Greece, Spain and Italy, where it is consumed in great quantities. Many studies have also demonstrated the cancer protective properties of carotenoids, a phytonutrient found in the red, orange and yellow pigments of fruits and vegetables. The NCI lists obesity as a risk factor for disease recurrence but does not recommend a specific diet for weight loss, although it has consistently recommended lowering dietary fat to prevent breast cancer.
Flynn developed the olive oil diet used in the study, which included at least three tablespoons of olive oil per day, with nuts at breakfast. Women also ate three servings of fruit and unlimited vegetables daily, and whole grains were also emphasized. Women could eat limited amounts of poultry and fish per week but red meat and polysaturated fats, like vegetable oils, were prohibited.
Because the NCI-recommended low-fat diet is not as specific, women had a less restrictive meal plan. Their diet consisted of at least five servings of fruits and vegetables, approximately 25 to 50 grams of fat (including canola oil) and six to seven ounces of lean meat (not red meat) daily.
The study included 44 overweight women (BMI of at least 25) diagnosed with invasive breast cancer after the age of 50 who were within four years after completing treatment. The order of the diets was randomly assigned, and participants followed each diet for eight weeks. Women were provided with meal plans and recipes for each diet and were asked to keep three-day food diaries at weeks four and eight of each diet and during months three and six of the follow-up period. Weight was measured and blood samples were taken at the end of each study period.
Overall, 28 of the 44 women completed both diets and 19 of the 22 eligible for the six months of follow-up chose to follow the plant-based olive oil diet. All 19 women either maintained their weight loss or lost additional weight during this time.
"I found this surprising, particularly since the low-fat diet is more commercial and more recognizable to women, so I thought the preference would be more evenly split," says Flynn, who is also an assistant professor of medicine at The Warren Alpert Medical School of Brown University. "But the women who enjoyed the olive oil diet said not only were they losing weight but they weren't as hungry. That's because they were advised to include fat in the form of olive oil or nuts at each meal, so they weren't as likely to snack between meals, which can cause weight gain."
As researchers expected, the plant-based olive oil diet also resulted in lower triglycerides (a type of fat found in the blood) and higher high-density lipoprotein cholesterol (HDL, or "good" cholesterol). High triglycerides and low levels of HDL have both been linked with increased cancer risk.
The study was supported by a grant from The Susan G. Komen for the Cure Foundation. Steven E. Reinert, MS, from Lifespan Information Services, was co-author on the study.
Source: Lifespan
Copyright: Medical News Today
Scientific Proof helps us promote our Before Forty Campaign...
Breast Cancer Screening: MRI Sensitive, No Added Value With Mammography, Study Suggests
ScienceDaily (Mar. 8, 2010) — Do we need a revision of current recommendations for breast cancer screening? According to a recent prospective multicenter cohort study published in the Journal of Clinical Oncology, this appears advisable at least for young women carrying an increased risk of breast cancer. The results of the EVA trial confirm once more that magnetic resonance imaging (MRI) is substantially more accurate for early diagnosis of breast cancer than digital mammography or breast ultrasound: MRI is three times more sensitive for breast cancer than digital mammography.
For the EVA trial, almost 700 women were enrolled. Aim of the trial was to refine existing guidelines for surveillance of women at high and moderately increased risk of breast cancer. Findings suggest that in these women, MRI is essential for early diagnosis -- and that a mammogram or an ultrasound examination does not increase the "cancer yield" compared to what is achieved by MRI alone. Researchers conclude that annual MRI is not only necessary, but in fact sufficient for screening young women at elevated risk of breast cancer. In women undergoing screening MRI, mammograms will have no benefit and should be discontinued. Moreover, MRI screening is important not only for women at high risk, but also for those at moderately increased risk.
Between 2002 and 2007, the EVA trial recruited 687 women who carried a moderately increased risk of breast cancer (lifetime risk of 20% and over). Women underwent 1679 screening rounds consisting of annual MRI, annual digital mammography and half-annual screening ultrasound examinations. During this time span, 27 women received a new diagnosis of invasive cancer or DCIS (Ductal Carcinoma In Situ).
Of all imaging methods under investigation (digital mammography, ultrasound and MRI), MRI offered by far the highest sensitivity: MRI identified 93% of breast cancers. 37% of cancers were picked up by ultrasound. The lowest sensitivity was achieved by digital mammography, which identified only one-third of breast cancers (33%). These results confirm once more that MRI is essential for surveillance not only of women at high risk, but also for women at moderately increased risk of breast cancer. Moreover, the results contradict current guidelines according to which mammography is considered indispensable for breast cancer screening. One aim of the EVA trial was to question this concept and to ask whether it is still appropriate to require that MRI should only be used in addition to mammography. The results speak for themselves: If an MRI is available, then the added value of mammography is literally negligible. Researchers conclude that MRI is necessary as well as sufficient for screening young women at elevated risk of breast cancer. Since mammography appears to be unnecessary in women undergoing MRI, its use is no longer justifiable, and current guidelines should be revised to reflect this.
Current guidelines questionable
Current guidelines for women at high familial risk of breast cancer recommend annual MRI (with or without ultrasound) and annual MRI starting at age 25-30. "These guidelines were set up based on little or no scientific evidence, and mainly reflect expert opinion," summarizes Prof. Christiane Kuhl, radiologist at the University of Bonn and principal investigator of the EVA trial. "In the light of the results of the EVA trial, such recommendations should be revisited." This seems even more important because digital mammography uses x-rays (ionizing radiation) to detect breast cancer. "The radiation dose associated with regular mammographic screening is clearly acceptable and safe," underscores Kuhl. "However, regular mammographic screening usually starts at age 40-50." The situation is different if systematic annual mammographic screening is started at age 25-30. "Not only because these women will undergo more mammograms and therefore will experience a cumulative lifetime radiation dose that will be substantially higher, but also because the breast tissue of young women is more vulnerable to the mutagenic effects of radiation." This appears to be especially true for BRCA mutation carriers. "Accordingly, we impose more radiation on less radiation-tolerant breast tissue -- for a very limited, if any, diagnostic benefit." Therefore, Kuhl advocates a revision of existing guidelines: "It is no longer justifiable to insist on annual mammographic screening women in their thirties if they have access to screening MRI."
MRI is a mature technology
In the past, MRI was used strictly in addition to mammography only. The allegedly high rate of "false positive" diagnoses and the allegedly insufficient sensitivity for DCIS were the main reason to discourage its use as a stand-alone method for breast cancer screening. "In this multicenter trial, with basic quality assurance implemented not only for mammography, but also for MRI, we were able to prove that false positive diagnoses are avoidable if MRI studies are interpreted with adequate radiologist expertise." In the EVA cohort, the Positive Predictive Value achieved with MRI was already even higher than that of mammography or breast ultrasound. "Moreover, we found that MRI offered the highest sensitivity especially for DCIS," adds Dr. Kuhl. "It is simply wrong to state that we need a mammogram to detect intraductal cancer."
Kuhl et al. Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial. Journal of Clinical Oncology, 2010; DOI: 10.1200/JCO.2009.23.0839
Targeted therapy for TNBC...this could be big
This could be big. Breast cancer is not one disease as we all know. Triple Negative Breast Cancer has been on the back burner in terms of new therapies, until now. PARP treatment is changing the future of metastatic TNBC patients. Now, a new, targeted therapy has identified a sub-type of TNBC tumors...
New Subtype of Breast Cancer Responds to Targeted Drug
ScienceDaily (Mar. 2, 2010) — A newly identified cancer biomarker could define a new subtype of breast cancer as well as offer a potential way to treat it, say researchers at Washington University School of Medicine in St. Louis.
Their findings will be published in the March 1 online early edition issue of the Proceedings of the National Academy of Sciences.
The research could further refine what recent breast cancer research has concluded: that breast cancer is not one disease, but many. So far, research has firmly established that at least five subtypes of breast cancer exist, each having distinct biological features, clinical outcomes and responses to traditional therapies.
The biomarker identified by the Washington University researchers is found frequently in breast cancers and especially in those that have poorer outcomes. It stems from overactivation of a gene called LRP6 (low-density lipoprotein receptor-related protein 6), which stimulates an important cell-growth signaling pathway. LRP6 can be inhibited by a protein discovered in the same laboratory, which could become an effective drug against the breast cancer type, the researchers say.
"We found increased expression of the LRP6 gene in about a quarter of breast cancer specimens we examined, and we think LRP6 overexpression could be a marker for a new class of breast cancer," says Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. "In addition, we found that this biomarker is often associated with breast cancers that are either harder to treat or more likely to recur. We already have an agent that seems to be effective against LRP6-overexpressing tumors, which could someday become a therapy for tumors that right now have few treatment options."
The research was conducted primarily by Chia-Chen Liu, a graduate student in the Bu lab, who is a fellow in the Cancer Biology Pathway Program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.
The researchers' analysis of human breast cancer tissue samples found significant increases in LRP6 levels in 20 percent to 36 percent of the tumors. LRP6 was increased more frequently in ER (estrogen receptor)-negative or HER2 (human epidermal growth factor receptor 2)-negative samples. LRP6 was also increased more frequently in so-called triple-negative breast tumor samples, which test negative for ER, HER2 and PR (progesterone receptor).
In general, patients who have triple-negative breast cancers have an increased risk of disease recurrence after initial treatment and a poorer prognosis. Furthermore, although ER-positive and HER2-positive tumors can be targeted with specific therapies, ER-negative and HER2-negative tumors cannot. So it appears that LRP6 overexpression is often associated with tumors that are currently difficult to treat, says Bu.
Research in the lab had earlier discovered a protein that binds to and inhibits LRP6. This study showed that the protein, called Mesd (mesoderm development), was able to slow the growth of breast cancer cells in the laboratory and to inhibit mammary tumor growth in laboratory mice.
Importantly, mice treated with Mesd did not experience any of the known side effects, such as bone lesions, skin disorders or intestinal malfunctions, associated with inhibition of this growth pathway.
"Our work introduces Mesd as a promising antitumor agent that might be further developed for breast cancer therapy," Bu says. "It would be analogous to such successful breast cancer therapies as Herceptin (trastuzumab), which specifically targets HER2-positive breast cancer."
The researchers also found that a small segment of Mesd has the same effect as the larger molecule. This segment, or peptide, is more stable than the whole protein molecule and can be easily synthesized.
The researchers have patented the protein and the peptide through the university's Office of Technology Management. Recently, Raptor Pharmaceutical Corp. licensed Mesd from the university to develop it for clinical use.
Funding from the National Institutes of Health and the Siteman Cancer Center supported this research.
Got Hope? TNBC patients do now!
The Reviews Are in:
Blockbuster drug known as PARP = A future of hope
"I believe that in the next two to three years, PARP inhibitors will do for triple-negative breast cancer what trastuzumab [Herceptin] did for HER2 breast cancer." Jenny Chang, Baylor
"This development may have the potential to change patient survival . . . and appears to potentially change the natural history of at least a subclass of metastatic breast cancer [TNBC]" Clifford Hudis, MSK
“When you go home, be excited. Be really excited about this. Tell your patients there is reason to be hopeful.” Eric Winer, Dana Farber
Until now, the treatment for triple negative breast cancer has been limited. The options for metastatic patients were few and far between. Until now. The first completed studies of PARP, have shown that not only does it slow progression of disease, but patients are experiencing a complete response to the drug.
The side effects of PARP are generally well tolerated and do not include hair loss.
Where once there was no hope, no magic drug for triple negative patients, PARP is proving itself to be, as Dr. Jenny Chang, of the Baylor School of Medicine said, “What Herceptin did for HER2 breast cancer.”
“Many experts have argued that it is not possible to change survival in stage IV breast cancer. Certainly now there evidence for an alternative viewpoint; that with the use of very effective drugs, we can change overall survival, and we should aim for that." Clifford Hudis, MSK
For more information, speak to your oncologist. For information on recruiting trials for PARP click the following links:
http://clinicaltrials.gov/ct2/show/NCT00664781?term=PARP&rank=3
http://clinicaltrials.gov/ct2/show/NCT00516724?term=PARP&rank=4
http://clinicaltrials.gov/ct2/show/NCT00647062?term=PARP&rank=6
Sources:
Chang C. Interview with Neil Love. in Conversations with Oncology Investigators - Bridging the Gap between Research and Patient Care. Breast Cancer Update 2009;8(6):3-6 [Track 5; with audio].
Hudis C. Interview by L Scott Zoeller 2009 Oct 21. Extended Survival With PARP Inhibitors Changes Expectations in Metastatic Breast Cancer. Viewpoints. In OncologySTAT 2009.
Carlson R. PARP Inhibitors Show Promise Against Metastatic Triple-Negative Breast Cancer in Early Studies. Oncol Times 2009;31(15):10-11.
Genomic project zeroes in on TNBC...
Triple Negative Breast Cancer News: Genome Project
Background: Drug companies have developed an array of drugs to attack cancer and other conditions influenced by genetics, but it’s difficult to tell which patients will respond to which drugs.
What’s happening: A new study will sequence the genomes of cancer tissue from 14 breast cancer patients whose tumors have progressed despite multiple treatments.
The future: Proponents of “genomic medicine” think it will become increasingly possible to use sequencing to steer individual patients to the drugs most likely to work.
A Carlsbad biotechnology company is helping launch an unusual cancer study that may eventually lead to doctors tailoring treatments to patients’ genes. Life Technologies says the study — involving sequencing the genomes of 14 patients with a tough-to-treat form of breast cancer — is a step toward a future of “genomic medicine,” a decade after the sequencing of the first human genome.
It’s evidence of how quickly work in this area is progressing, with the $2.6 billion that went into the Human Genome Project reduced to $6,000 per genome on Life Technologies’ latest sequencing instrument. “This is a pretty amazing example of how far these tools of genomics are moving into direct patient applications,” said Jeffrey Trent, president of the Phoenix-based Translational Genomics Research Institute, which is working with Life Technologies on the project.
The company will announce the study today to coincide with the opening of a two-day conference on genomic medicine in La Jolla, at which experts will discuss the latest breakthroughs and the outlook for more advances in the field. Already, biotechnology research has created numerous drugs that target genetic problems that lead to cancer and other conditions. In the case of breast cancer, at least a dozen such drugs are on the market, said Dr. Daniel
D. Von Hoff, physician-in-chief at the translational genomics institute. A big problem, however, is that it’s difficult to predict which drugs will work for a particular patient. That’s where sequencing is supposed to help.
“For those mutations for which we do have drugs, we can help the physician make more informed decisions than they’re making today,” said Linh Hoang, director of personalized medicine at Life Technologies.
The study could also help scientists identify promising areas to explore for future drugs. It’s impossible to know ahead of time whether the 14 patients have genetic patterns that current drugs address, but researchers will also look for similarities in the DNA of the 14.
“It may lead to more targets that pharmaceutical companies will want to design drugs around,” Hoang said.
The study will involve patients with what’s known as triple-negative breast cancer whose tumors have progressed despite multiple therapies. That type of cancer makes up about a fifth of breast cancer cases and doesn’t respond to common drugs, such as Herceptin. Patients will be enrolled by U.S. Oncology, a Houston-area company that specializes in cancer-treatment services, and Von Hoff said the plan is to take the first 14 people who meet the study criteria.
A spokeswoman for U.S. Oncology said the company plans to enroll patients from about a half-dozen of its sites with the highest incidences of triple-negative cases. Sites in Colorado, Oregon, Texas and Virginia have already been identified.
Tissue samples will be obtained through noninvasive surgery, Von Hoff said. Then the patients will go home to await sequencing results that should be produced within a few weeks.
The idea is to then direct them to appropriate treatment, but Von Hoff declined to predict in how many cases that will be possible. “We don’t know,” Von Hoff said. “We do know there are more and more drugs out there for patients who have mutations.”
There have been other studies that sequenced disease tumors, most notably an ongoing government effort known as the Cancer Genome Atlas that aims to produce comprehensive genetic maps of at least 20 types of cancer.
What separates the new study is its attempt use the data to drive treatment strategies, not merely to collect information “It’s a different question,” the genomics institute’s Trent said. “This is a study about how we’re going to start to use this in a precision medicine approach.”
A big effort will go into “bioinformatic” analysis, which Von Hoff said will involve a trillion pieces of data per patient. Hoang said one project in lung cancer found 30,000 mutations.
In coming years, scientists expect the cost of sequencing to decline and the sophistication of the tools to improve to the point that sequencing becomes more viable as a diagnostic device.
Hoang said Life Technologies expects the cost of the reagent chemicals that it sells, which enable genome sequencing, to drop from $6,000 to $3,000 by the end of the year. “This is really laying the foundation for a future that may take five or 10 years to materialize,” Hoang said. “But it is truly groundbreaking.”
THOMAS KUPPER, UNION TRIBUNE, Uniontrib.com
When to Consider prophylactic bilateral mastectomy...
Contralateral Prophylactic Mastectomy Associated With Survival in Select Breast Cancer Patients
ScienceDaily (Mar. 3, 2010) — Contralateral prophylactic mastectomy (CPM), a preventive procedure to remove the unaffected breast in patients with disease in one breast, may only offer a survival benefit to breast cancer patients age 50 and younger, who have early-stage disease and are estrogen receptor (ER) negative, according to researchers at The University of Texas M. D. Anderson Cancer Center.
Published online February 25 in the Journal of the National Cancer Institute, it's the first population-based study to find an association between the procedure and survival in any group of breast cancer patients. The findings should offer evidence to both the women making this often agonizing decision and the physicians responsible for their care.
According to Isabelle Bedrosian, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology, a growing number of breast cancer patients are opting for the procedure; recent statistics have shown that the rate of CPM in women with stage I-III breast cancer increased by 150 percent from 1998 to 2003 in the United States.
"In our clinic, we've seen a dramatic increase in the number of women requesting CPM, and across the breast cancer community, studies have shown that the utilization of the procedure is skyrocketing," said Bedrosian, the study's co-corresponding author. "Until now, we've counseled these patients on a very important, personal decision in a vacuum. With our study, our goal was to understand the implications of the surgery and who may benefit."
For the retrospective, population-based study, the researchers used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry now representing 26 percent of the country's population, to identify 107,106 breast cancer patients who underwent a mastectomy for treatment, as well as a subset of 8,902 women who had CPM. All of the women were treated for stages I -- III breast cancer between 1998 and 2003. Patients were stratified for ER status, stage of disease and age. Breast cancer-specific survival served as the study's primary endpoint.
Rigorous analysis was paramount in the design of the study, said George J. Chang, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology.
"It was important to take a critical eye and look at all the different ways the data could be misinterpreted to ensure that biases were not impacting our findings," said Chang, the study's co-corresponding author. "Using multi-variable analysis as well as risk stratification, we did our analysis in many different ways -- through SEER, comparing the survival of these patients to that of the general population, as well as examining non-cancer related versus cancer-specific survival. All alternative analyses resulted in the same conclusion; we found one group for whom this surgery offers a true survival benefit."
The researchers found a clear survival benefit for a select group of women that represents less than 10 percent of the breast cancer population. Those younger than age 50 with stage I or II cancer with ER negative disease had a survival benefit of 4.8 percent at five years. However, both Bedrosian and Chang expect that future research will show increased survival benefit with longer follow-up in the population, as a patient's likelihood of getting a second breast cancer increases with time.
While the findings should serve as a guideline for breast cancer patients and their physicians to have an informed, medically-based discussion about CPM, they do not determine that CPM is medically inappropriate for all others with the disease, said the researchers.
"Our research found that breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM," said Bedrosian. "However, there are other populations -- such as women between the age of 50 and 60 -- where the findings about the procedure remain less clear. In addition, for young women with early stage, estrogen receptive positive breast cancer who receive Tamoxifen for only five years, we really do not know whether they would derive a life-long protective effective from a second breast cancer event. Therefore, for some additional breast cancer patients, CPM may very well be a medically-appropriate option."
In addition, the researchers note, the study captured neither family history nor BRCA status; it also did not include DCIS, or stage 0 breast cancer patients.
In addition to Bedrosian and Chang, Chung Yuan Hu in the Department of Surgical Oncology, also authored the all-M. D. Anderson study.
Pomegranate Therapy...
Natural Compounds in Pomegranates May Prevent Growth of Hormone-Dependent Breast Cancer
ScienceDaily (Jan. 6, 2010) — Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.
"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.
Previous research has shown that pomegranate juice -- punica granatum L -- is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.
Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.
After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.
"We were surprised by our findings," said Chen. "We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different."
According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.
"This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells," said Stoner, who is not associated with this study. "It's not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet."
Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.
Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner's sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.
"More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention," Brown said. "This study does suggest that studies of the ellagitannins from pomegranates should be continued."
Until then, Stoner said people "might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs."
DCIS News
Trial Launched to Test New Treatment for Pre-Invasive Breast Cancer
ScienceDaily (Mar. 2, 2010) — Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That's what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI) are trying to prove.
In January, the IBCI and CAPMM launched the PINC Trial, short for Preventing Invasive Breast Neoplasia with Chloroquine. This three-year clinical trial will test the effectiveness of the anti-malarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal.
With an estimated 254,650 patients diagnosed in 2009 alone, breast cancer is the most common form of cancer in women according to statistics by the American Cancer Society. Approximately one quarter of those patients will have DCIS. Many more women are being diagnosed with DCIS, non-invasive breast cancer, with the routine use of screening mammography.
According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing pre-invasive cancer cells using a novel therapy with chloroquine, which has been used to treat malaria in the past.
"We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In pre-clinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. "What this trial is proposing is to treat DCIS patients with chloroquine, an autophagy blocker before they receive standard of care surgery to treat their DCIS disease. We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS. We may be able to prevent someone from needing a mastectomy and offer them breast conserving surgery."
Once patients have consented and enrolled, the size of their breast tumor will be measured through a non-invasive imaging technique called magnetic resonance imaging (MRI). Tissue samples will be taken from patients by Inova's doctors and transported to CAPMM for analysis. The PINC trial will combine chloroquine with Tamoxifen depending on the patient's tumor profile. After treatment, the MRI will be repeated to see if the tumor has shrunk and the patient will then proceed with surgery and follow up therapy.
What made the researchers think to use a malaria drug to treat breast cancer? According to Ginny Espina, a CAPMM research assistant professor, it works by starving the cancerous cells.
"Pre-cancerous cells have adapted to survive inside the milk duct without a blood supply and with very few nutrients. They overcome starvation through a process called autophagy. It's a way for a cell to make its own food and store it in a 'cookie jar.' In the breast ducts, the DCIS cells use these 'cookies' to survive and potentially spread. Simply put, chloroquine goes into the cell's 'cookie jars' and prevents the cells from using that food so that they eventually die from starvation," says Espina.
Of note, researchers are also using chloroquine in patients with unique types of brain tumors.
The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy.
"I think the most exciting thing is that we are able to offer women a new clinical trial using a well tolerated therapy in a new way to help prevent the development of invasive breast cancer and hopefully, ultimately, it will keep them from needing any additional treatment or surgery," says Edmiston. "We look forward to a future where all breast cancer can be prevented or destroyed."
The clinical study is being funded by George Mason University and Inova Health System. This study is based on scientific findings made under a Department of Defense funded breast cancer grant to George Mason University (Lance Liotta MD, PhD) in partnership with Inova.
Her2 News...
Neoadjuvant Chemotherapy With Trastuzumab Followed by Adjuvant Trastuzumab Versus Neoadjuvant Chemotherapy Alone, in Patients With HER2-Positive Locally Advanced Breast Cancer (the NOAH Trial)
Lancet. 2010 Jan 30;375(9712):377-384, L Gianni, W Eiermann, V Semiglazov, A Manikhas, A Lluch, S Tjulandin, M Zambetti, F Vazquez, M Byakhow, M Lichinitser, MA Climent, E Ciruelos, B Ojeda, M Mansutti, A Bozhok, R Baronio, A Feyereislova, C Barton, P Valagussa, J Baselga
Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer
Supplementary editorial provided by OncologySTAT
TAKE-HOME MESSAGE
Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer.
EXPERT COMMENTARY
Lee Schwartzberg, MD, Editor-in-Chief Oncology Stat
In HER2-positive breast cancer, adding trastuzumab to chemotherapy yields impressive benefit in both the adjuvant and metastatic setting and is the standard of care. The current trial fills in the gaps by providing randomized clinical trial evidence of a 41% improvement in event-free survival when trastuzumab was given to patients with HER2-positive locally advanced or inflammatory breast cancer in the neoadjuvant setting. Particularly noteworthy in this NOAH trial was the use of every-3-weeks dosing of trastuzumab from initiation of treatment, a low cardiac event rate despite concurrent adriamycin/trastuzumab therapy, and a marked benefit recorded in the inflammatory breast cancer group of a 73% improvement in event-free survival.
ABSTRACT
Background: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.
Methods: We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.
Findings: Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61–78; n=36 events] with trastuzumab, vs 56% [46–65; n=51 events] without; hazard ratio 0•59 [95% CI 0•38–0•90]; p=0•013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.
Interpretation: The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.
Copyright © Elsevier Inc. All rights reserved
PARP Props...
PARP Inhibition Could Have Broad Application
Elsevier Global Medical News February 2010
Lee Schwartzberg is Senior Partner and Medical Director, The West Clinic, Memphis, TN.
1. In your view, which development in breast cancer that has occurred in 2009 could have the most significant impact on oncology?
The development in 2009 with the potential for the most impact was the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors as a new class of agent for the treatment of malignancies. Reports this year confirmed both single-agent activity of PARP inhibitors and synergy with chemotherapy. Moreover, the benefit was highly significant, leading to better overall survival in one small randomized trial.1
2. What specific changes in oncology have you observed or do you foresee as a result of this development?
If results hold up, PARP inhibition will be the first systemic therapy designed for hereditary cancers that contain a somatic mutation responsible for the malignancy, specifically BRCA1 or BRCA2 mutations. Patients with these mutations lack functional BRCA proteins, which are important in normal DNA repair, and thus they develop cancers. More broadly, there is exciting evidence of benefit from PARP inhibition in triple-negative breast cancer, an aggressive subtype for which there is currently no specific therapy.
3. Could you put this development into historical perspective for the practicing oncologist?
While PARP enzymatic function as a DNA repair mechanism has been recognized for some time, what is new is the idea that inhibition of this pathway in cells where alternative repair systems (such as BRCA) have already been damaged could lead to cancer cell death. This concept is termed synthetic lethality. This could represent a paradigm shift leading to exploration of similar approaches in other critical cellular pathways.
4. Would you sum up in a single sentence why you chose this development as the top story of the past year?
PARP inhibition capitalizes on a central and critical function of malignant tissue, DNA repair, and has already shown strong evidence of benefit. This class of drugs could have broad application in treating other cancers as well.
Reference
1. O'Shaughnessy J, Osborne C, Pippen J, et al. Final results of a randomized phase II study demonstrating efficacy and safety of BSI-201, a Poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with gemcitabine/carboplatin (G/C)in metastatic triple-negative breast cancer (TNBC) (abstract 3122). Presented at 32nd San Antonio Breast Cancer Symposium 2009; San Antonio, TX; December 10-13, 2009.
© ONCOLOGYSTAT 2010
It's not you, it the treatment...
Decline in Breast Cancer Mortality Means Increase in Chronic Symptoms
Elsevier Global Medical News. 2008 Jan 17, B. Jancin
SAN ANTONIO (EGMN) - The other side of the impressive decline in breast cancer mortality during the last several decades is the unprecedented number of survivors with tough to control chronic symptoms caused by the disease or its aggressive therapy, Dr. Charles L. Loprinzi said at the San Antonio Breast Cancer Symposium.
He focused on evidence-based therapies of five of the most common and problematic breast cancer survivorship issues: vaginal dryness, fatigue, chemotherapy-induced neuropathy, diminished libido, and hot flashes.
Vaginal dryness: Pilocarpine shows enough promise that Dr. Loprinzi and colleagues have embarked on an ongoing randomized, double-blind, placebo-controlled trial of the oral drug at 5 mg once daily or b.i.d. in 192 women treated for breast cancer. Results should be available next year.
The impetus for the study was an anecdotal report a few years ago of marked clinical improvement in cyclophosphamide-induced vaginal dryness in four patients, along with a separate earlier report of significantly decreased vaginal dryness as a secondary outcome measure in a phase III trial of pilocarpine for oral and ocular dryness in patients with Sjögren's syndrome (Arch. Intern. Med. 1999;159:174-81). The drug is approved for that indication as well as for dry mouth caused by head and neck radiation therapy.
Estrogen therapy is effective for vaginal dryness and is worthwhile in some severely affected women, but there is concern that it could promote breast cancer recurrence. That concern extends to vaginal estrogens as well.
"All of the vaginal agents, in my mind, do lead to systemic levels of estrogen in some patients," said Dr. Loprinzi, professor of medicine and chair of oncology at the Mayo Clinic, Rochester, Minnesota.
Nonestrogenic vaginal lubricants are "somewhat effective," but are clearly inferior to estrogen in comparative studies, he added.
Fatigue: This is a major complaint for cancer patients across the full spectrum of disease, from those on adjuvant chemotherapy to patients with advanced, incurable cancer. Exercise is the intervention with the strongest evidence base.
"Exercise is the answer, not more rest," Dr. Loprinzi emphasized.
Modafinil, donepezil, L-carnitine, and methylphenidate have been looked at in pilot studies, but more work is needed before any of them can be recommended for cancer-related fatigue.
Similarly, Dr. Loprinzi and coworkers were encouraged by the results of their pilot 8-week, double-blind dose-finding study of American ginseng, in which roughly 25% of cancer patients on 1,000 or 2,000 mg/day of ginseng reported their fatigue was moderately to very much better, compared with 10% on placebo.
"The evidence isn't there to recommend ginseng for use at this time, but we're excited about it. The toxicity profile looked very favorable. We're about to start a larger placebo-controlled trial," the oncologist said.
Chemotherapy-induced neuropathy: Gabapentin is widely prescribed for this problem. However, the sole rigorous study to date - a multicenter, placebo-controlled, double-blind, crossover trial conducted by Dr. Loprinzi and colleagues in the North Central Cancer Treatment Group (NCCTG) - failed to demonstrate any benefit (Cancer 2007 Nov. 1;110:2110-8).
Vitamin E (alpha-tocopherol) at a dose of 400 mg/day was reported to protect against cisplatin-induced peripheral neuropathy and ototoxicity in an interim analysis of a 50-patient randomized, placebo-controlled study presented at last year's American Society of Clinical Oncology meeting. The NCCTG has an ongoing randomized trial, also comparing vitamin E at 400 mg/day and placebo. Until the results are in, Dr. Loprinzi urged caution in using vitamin E for prevention of chemotherapy-induced neuropathy.
"We haven't proved that it's helpful, number 1, and also there are some data suggesting that vitamin E can get in the way of cytotoxic therapy, particularly radiation therapy for the head and neck area. Maybe that will also apply to chemotherapy. We need to sort all this out," he said.
Low libido: Sexual counseling is the only thing that can be recommended. Transdermal testosterone cream proved ineffective in a double-blind, randomized, placebo-controlled crossover trial conducted by Dr. Loprinzi and the NCCTG (J. Natl. Cancer Inst. 2007 May 2; 99:672-9).
Testosterone did improve low libido in several prior studies in women without cancer. The most likely explanation for the disparate results lies in the fact that all participants in those studies were either premenopausal or on estrogen replacement therapy; in contrast, the cancer patients weren't receiving estrogen, he noted.
Hot flashes: Effective nonhormonal therapies are available. Dr. Loprinzi and his colleagues showed in a randomized, double-blind, placebo-controlled trial that venlafaxine at 37.5 or 75 mg/day reduced hot flash scores by 40% and 60%, respectively, from baseline (Lancet 2000; 356:2059-63).
In a subsequent double-blind, placebo-controlled crossover trial, they demonstrated that fluoxetine at 20 mg/day also was effective in reducing hot flashes in women with a history of breast cancer (J. Clin. Oncol. 2002;20:1578-83), although it appears to be less so than venlafaxine.
Paroxetine at 20 mg/day appears to be roughly as effective as venlafaxine at reducing hot flashes, based upon randomized controlled studies by other investigators. Sertraline at 50 and 100 mg/day doesn't seem to work as well as do the other antidepressants.
A couple of negative venlafaxine studies have been reported. However, neither featured adequate pretreatment baseline hot flash scores. That's a fatal methodologic flaw, according to Dr. Loprinzi, who noted that in his study that venlafaxine reduced hot flash scores by an average of 30% on day 1, compared with the baseline week.
Tamoxifen is metabolized by cytochrome P450 2D6 to a key active metabolite, endoxifen, which is believed to be responsible for the selective estrogen receptor modulator's efficacy in preventing breast cancer. Coadministration of paroxetine and tamoxifen has been reported to result in a significant decrease in plasma endoxifen levels (J. Natl. Cancer Instit. 2003;95:1758-64). In contrast, venlafaxine didn't reduce endoxifen levels in another study (Clin. Pharmacol. Ther. 2006;80:61-74).
Another nonhormonal option is gabapentin, which at 900 mg/day, significantly reduced hot flash scores in a placebo-controlled trial by investigators at the University of Rochester (Obstet. Gynecol. 2003;101:337-45).
Copyright © 2008 International Medical News Group
At last, they are coming to their senses...
New Mammogram Guidelines Issued ... Again
livescience.com Mon Jan 4, 3:16 pm ET
Breast cancer screening just got more confusing today, as two medical organizations announced annual mammograms should begin at age 40, and earlier for high-risk women. The recommendations contradict a recent advisory for less frequent screenings beginning at age 50, not 40.
The recommendations for less frequent mammograms, released in November, came from the U.S. Preventive Services Task Force, with panel experts saying they were responding to data showing routine mammograms starting at age 40 rarely saved lives and more often resulted in misdiagnoses that just fueled anxiety and debilitating treatment.
This new advice, which is published in the January issue of the Journal of the American College of Radiology, comes from the Society of Breast Imaging (SBI) and the American College of Radiology (ACR). And these groups suggest just the opposite - that the screening does save lives.
"The significant decrease in breast cancer mortality, which amounts to nearly 30 percent since 1990, is a major medical success and is due largely to earlier detection of breast cancer through mammography screening," said lead study author Dr. Carol H. Lee, a radiologist at Memorial Sloan-Kettering Cancer Center. "For women with the highest risk of developing breast cancer, screening technologies in addition to mammography have been adopted," said Lee, who is the chair of ACR's Breast Imaging Commission.
What's a woman to do? Regarding how women should follow the task force recommendations from November, Dr. Carl D'Orsi, director of Emory University's Breast Imaging Center, said, "As a bottom line, they should be ignored." D'Orsi was a member of the team that came out with today's recommendations.
Dr. Ned Calonge, chairman of the U.S. Preventive Services Task Force, had not responded to a request for an interview as of this writing.
Screening science
D'Orsi and his colleagues reviewed the results of several randomized trials in Europe and North America, which included nearly 500,000 women in total. The review of these studies showed a 26 percent reduction in breast cancer mortality.
"This is scientifically driven with data, unlike what the task force did," D'Orsi said.
While today's recommendations are consistent with those put out by other groups, including the American Cancer Society, the new ones include other imaging techniques in addition to mammography.
Here are some of the highlights:
- The average patient should begin annual mammograms at age 40, and high-risk patients should begin by age 30 but not before 25. A woman with certain mutations to the BRCA1 or BRCA2 genes would be considered a high-risk individual.
- Annual MRI (magnetic resonance imaging) starting by age 30 is recommended for carriers of deleterious BRCA mutations. Women who are considered to have at least a 20 percent lifetime risk for breast cancer based on family history should get annual mammograms and annual MRI starting at age 30 (not before age 25), or 10 years before the age of the youngest affected relative, whichever is later.
- Ultrasound, in addition to mammography, can be considered for high-risk women and those with dense breast tissue. While ultrasound isn't as sensitive as MRI to detecting breast cancer, D'Orsi said some women can't get an MRI due to their weight (those over 300 pounds) and other factors.
The U.S. Preventive Services Task Force, an independent government agency made up of 16 primary care physicians and public health specialists, in November recommended breast cancer screening every other year for women aged 50 to 74. They argued against routine screening before this age.
That was counter to their own guidelines from 2002, D'Orsi said.
"All of a sudden, with no new data - ignoring the fact that there are seven trials that demonstrate a drop in breast cancer mortality with use of mammography versus no mammography, plus that breast cancer mortality has dropped 30 percent - they come out with a recommendation that no screening be done at age 40 to 49," D'Orsi told LiveScience.
He added, "Basically they said nothing is good. Just wait until it breaks through your skin and we'll take care of it. That's what we did in 1940."
In fact, the task force did note a 15-percent reduction in mortality among those ages 40 to 49 who are screened," D'Orsi and colleagues wrote in their research paper. But they stated the harms outweigh the benefits. These harms include: anxiety over false positive results, the screening itself, need for additional testing or biopsy, and the possibility of overdiagnosis and overtreatment.
Why start screening at age 50? Essentially, years ago scientists began grouping women under and over age 50 into separate groups. And so when the age groups get compared, there are far fewer incidences of breast cancer in the younger group than in those 50 and older.
"Of course there's more breast cancer there, because it's age dependent," D'Orsi said. "That doesn't mean you don't screen. As a matter of fact those cancers [in the younger age group] are biologically more significant and may have a greater impact on life expectancy."
November, 2009
Government Panel Urges Change in Age from 40 to 50 for Mammograms-
A response
To save money, to reduce insurance costs and to reduce "Anxiety" a panel that guides the ACS has declared that women should skip mammograms until the age of 50, and then only have them every other year or so... because they don't do any good.... they cause too much anxiety....they cost too much.
Not having screening and having your cancer found too late costs a lot of money, too. It causes anxiety that is beyond all compare. And they can't do any good because your cancer is already spreading.
This blog post is dedicated to the women we have lost, only very few had the genetic cancer link that is exempt from this murderous recommendation. Most of these women were diagnosed before the age of 40 or in their early 40s. None of them are alive today.
Stephanie
Lisa
Amy
Denise
Mena
Susan
Susie
Lani
Lori
Deb
Ferne
Kay
Dawn
Annie
Julie
Twilah
Helen
Jodi
Kari Lynn
Cindy
Erin
Kathy
Cheryl
Lisa
Laura
Mary Ellen
Mabel
Donna
Marge
Jacque
Kathy
Fran
Vicky
Carla
Chris
Shelley
Julie
Leah
Connie
Shelli
Jayne
Ruth
Elena
Jen
Peggy
Kelly
Stacey
Diane
Bev
Theresa
Luann
Donna
Kathy
Diane
Roza
Kelly
Felicia
Stacy
Mildred
June
Sadie
Ann
Emmaline
Sprite
Breezy
Kay
Kathleen
Lanie
Charlotte
Tine
Annette
Janie
Frances
Bluekitten
Momcasey
Janell
Jane
Shirl
Mary
Andee
LuAnn
Theresa
Linda
Faye
Marie
Roza
Linda
Flo
Kathy
Kat
Karen
Mavy
Raven
Cherieboop
Ann
Pam
Nancy
In Reversal, Panel Urges Mammograms at Age 50, not 40
By Gina Kolata
Most women should start regular breast cancer screening at age 50, not 40, according to new guidelines released Monday by an influential group that provides guidance to doctors, insurance companies and policy makers.
The new recommendations, which do not apply to a small group of women with unusual risk factors for breast cancer, reverse longstanding guidelines and are aimed at reducing harm from overtreatment, the group says. It also says women age 50 to 74 should have mammograms less frequently — every two years, rather than every year. And it said doctors should stop teaching women to examine their breasts on a regular basis.
Just seven years ago, the same group, the United States Preventive Services Task Force, with different members, recommended that women have mammograms every one to two years starting at age 40. It found too little evidence to take a stand on breast self-examinations.
The task force is an independent panel of experts in prevention and primary care appointed by the federal Department of Health and Human Services.
Its new guidelines, which are different from those of some professional and advocacy organizations, are published online in The Annals of Internal Medicine They are likely to touch off yet another round of controversy over the benefits of screening for breast cancer.
Dr. Dianna Petitti vice chairwoman of the task force and a professor of biomedical informatics at Arizona State University said the guidelines were based on new data and analyses and were aimed at reducing the potential harm from overscreening.
While many women do not think a screening test can be harmful, medical experts say the risks are real. A test can trigger unnecessary further tests, like biopsies, that can create extreme anxiety. And mammograms can find cancers that grow so slowly that they never would be noticed in a woman’s lifetime, resulting in unnecessary treatment.
Over all, the report says, the modest benefit of mammograms — reducing the breast cancer death rate by 15 percent — must be weighed against the harms. And those harms loom larger for women in their 40s, who are 60 percent more likely to experience them than women 50 and older but are less likely to have breast cancer, skewing the risk-benefit equation. The task force concluded that one cancer death is prevented for every 1,904 women age 40 to 49 who are screened for 10 years, compared with one death for every 1,339 women age 50 to 74, and one death for every 377 women age 60 to 69.
The guidelines are not meant for women at increased risk for breast cancer because they have a gene mutation that makes the cancer more likely or because they had extensive chest radiation. The task force said there was not enough information to know whether those women would be helped by more frequent mammograms or by having the test in their 40s. Other experts said women with close relatives with breast cancer were also at high risk.
Dr. Petitti said she knew the new guidelines would be a shock for many women, but, she said, “we have to say what we see based on the science and the data.”
The National Cancer Institute said Monday that it was re-evaluating its guidelines in light of the task force’s report.
But the American Cancer Society and the American College of Radiology both said they were staying with their guidelines advising annual mammograms starting at age 40.
The cancer society, in a statement by Dr. Otis W. Brawley, its chief medical officer, agreed that mammography had risks as well as benefits but, he said, the society’s experts had looked at “virtually all” the task force and additional data and concluded that the benefits of annual mammograms starting at age 40 outweighed the risks.
Other advocacy groups, like the National Breast Cancer Coalition, Breast Cancer Action, and the National Women’s Health Network, welcomed the new guidelines.
“This is our opportunity to look beyond emotions,” said Fran Visco, president of the National Breast Cancer Coalition. The task force “is an independent body of experts that took an objective look at the data,” Ms. Visco said. “These are the people we should be listening to when it comes to public health messages.”
Some women, though, were not pleased. “I know so many people who had breast cancer and survived, and what saved their lives was early detection,” Janet Doughty, 44, of San Clemente, Calif., said in a telephone interview. She said she had had an annual mammograms since her late 30s and would not stop now.
The guidelines are not expected to have an immediate effect on insurance coverage but should make health plans less likely to aggressively prompt women in their 40s to have mammograms and older women to have the test annually.
Congress requires Medicare to pay for annual mammograms. Medicare can change its rules to pay for less frequent tests if federal officials direct it to.
Private insurers are required by law in every state except Utah to pay for mammograms for women in their 40s.
But the new guidelines are expected to alter the grading system for health plans, which are used as a marketing tool. Grades are issued by the National Committee for Quality Assurance, a private nonprofit organization, and one measure is the percentage of patients getting mammograms every one to two years starting at age 40.
That will change, said Margaret E. O’Kane, the group’s president, who said it would start grading plans on the number of women over 50 getting mammograms every two years.
The message for most women, said Dr. Karla Kerlikowske, a professor in the department of medicine, epidemiology and biostatistics at the University of California, San Francisco, is to forgo routine mammograms if they are in their 40s.
Starting at age 50, Dr. Kerlikowske said, “the message is to get 10 mammograms in a lifetime, one every two years.” That way they get the most benefit and the least harm from the test. If women are healthy, she added, they might consider having mammograms every two years until age 74.
Nearly two-thirds of all women in their 40s had mammograms within the last two years, as did 72 percent of women age 50 to 65, according to an editorial by Dr. Kerlikowske that accompanies the report.
In order to formulate its guidelines, the task force used new data from mammography studies in England and Sweden and also commissioned six groups to make statistical models to analyze the aggregate data. The models were the only way to answer questions like how much extra benefit do women get if they are screened every year, said Donald A. Berry, a statistician at the University of Texas M. D. Anderson Cancer Center and head of one of the modeling groups.
“We said, essentially with one voice, very little,” Dr. Berry said. “So little as to make the harms of additional screening come screaming to the top.”
The harms are nearly cut in half when women have mammograms every other year instead of every year. But the benefits are almost unchanged.
The last time the task force issued guidelines for mammograms, in 2002, the report was announced by Tommy G. Thompson, the secretary of health and human services. When the group recommended mammograms for women in their 40s, some charged the report was politically motivated. But Dr. Alfred Berg of the University of Washington, who was the task force chairman at the time, said “there was absolutely zero political influence on what the task force did.”
It was still a tough call to make, Dr. Berg said, adding that “we pointed out that the benefit will be quite small.” In fact, he added, even though mammograms are of greater benefit to older women, they still prevent only a small fraction of breast cancer deaths.
Different women will weigh the harms and benefits differently, Dr. Berg noted, but added that even for women 50 and older, “it would be perfectly rational for a woman to decide she didn’t want to do it.”
Researchers worry the new report will be interpreted as a political effort by the Obama administration to save money on health care costs.
Of course, Dr. Berry noted, if the new guidelines are followed, billions of dollars will be saved.
“But the money was buying something of net negative value,” he said. “This decision is a no-brainer. The economy benefits, but women are the major beneficiaries.”
Scientists have found a faulty gene linked to half of all breast cancers which experts have hailed as the most important discovery in the disease since the 1970s.
Rebecca Smith, Medical Editor Published: 11:39AM BST 05 Oct 2009
The finding will help researchers understand how cancer develops and may in future lead to new treatments, they said.
Everyone is born with the gene, called NRG1, but in some people it gets damaged during their lifetime and this can lead to cancer developing, it has been found.
Damaged NRG1s have been found in half of breast cancers and it has also been implicated in half of all prostate and bowel cancers along with one quarter of ovarian and bladder cancers.
When the gene works properly it acts as a brake, stopping cancer cells from growing, but when it is damaged the brakes are off, allowing the cells to multiply into a tumour.
Everybody is born with an intact NRG1 but it gets damaged in some people during their lifetime, thereby enabling cancer to develop.
The exact reason why the gene is damaged is lost has not yet been discovered.
However, by identifying the gene, experts hope they will be able to target therapies at specific cancers in the future.
The discovery of NRG1 is the most significant step forward in cancer gene research since another gene, p53, was discovered in the 1970s and was later implicated in the development in cancer in the 1980s.
This was the first "tumour suppressor" gene found within cells and it is now known that p53 is faulty or inactivated in many cancers.
The discovery was described as a "major step forward" by cancer charities in working out how cancer develops.
Dr Paul Edwards, of the department of pathology at the University of Cambridge, who discovered the gene with colleagues, said it provided "vital information" about how some cancers spread.
He said: "I believe NRG1 could be the most important tumour suppressor gene discovery in the last 20 years as it gives us vital information about a new mechanism that causes breast cancer.
"We found the gene on chromosome 8 partly by good luck and partly by good judgment.
"In every case that we looked at where a big chunk of chromosome 8 had been lost, at least part of the gene was lost.
"The gene was effectively 'turned off' in a lot of breast cancers.
"If we have found the gene that is lost on chromosome 8 and we know that some other cancers also lose that bit of chromosome 8, then it is logical that it is the same gene.
"We have got strong evidence that the gene is implicated in breast cancer but we have no reason to think it's not the same for other cancers, including prostate and colon cancer."
The research was published in the journal Oncogene and funded by Breast Cancer Campaign and Cancer Research UK.
Arlene Wilkie, director of research and policy at Breast Cancer Campaign, said: "Knowing the identity of this gene will lead to far more detailed studies of how it works and how it is involved in breast cancer development.
"This research is a major step forward in understanding the genetics of cancer and could open up a host of new strategies to improve diagnosis and treatment.
"In the UK, 12,000 women die from this disease every year, so it is vital we understand how breast cancer develops in order to stop it happening."
Lesley Walker, director of cancer information at Cancer Research UK, said: "This discovery is an important step forward in understanding a disease that more than 45,500 women are diagnosed with in the UK each year.
"It might then be possible to develop ways to bypass the gene or target treatments to the defect."
Aromatase Inhibitors and Joint Pain: A Deeper Look
Nick Mulcahy
September 23, 2009 — One third of postmenopausal women with breast cancer taking aromatase inhibitors (AIs) reported arthralgia — either new onset or worsening, according to investigators of a new study published online September 14 in the Journal of Clinical Oncology.
This percentage of patients experiencing joint pain was "expected," according to an editorial accompanying the study.
However, the study authors did not stop at investigating the prevalence of AI-associated arthralgia.
Because "few studies" have investigated the morphologic changes in joints and tendons in patients with this pain, the study authors used sonographic and electrophysiologic measurements to take a look at the affected tissues.
Nevertheless, the new study does not authoritatively correlate the findings from sonography and electromyography with clinical findings, observes the editorialist, Rowan T. Chlebowski, MD, PhD, from the Los Angeles BioMedical Research Institute at Harbor UCLA Medical Center in Torrance, California.
For instance, patients in the study with AI-related arthralgia had more frequent electrophysiologic findings of carpal tunnel syndrome (46% vs 20%; P < .05) than those without arthralgia (including those taking and those not taking AIs).
However, this 49% incidence of carpal tunnel syndrome in patients with AI-associated arthralgia is much higher than when the syndrome is identified through clinical symptoms. In large clinical trials of AIs and tamoxifen, the incidence of carpel tunnel syndrome was less than 3% for patients taking the AIs, Dr. Chlebowski notes.
The authors of the new study acknowledge that "the real prevalence of carpel tunnel syndrome would have been different if the signs and symptoms [had] been taken into consideration."
Very few patients discontinue treatment because of arthralgia.
AI-associated arthralgia is a "substantial problem" and one in need of "improved interventions," Dr. Chlebowski writes.
However, the editorialist and the study authors agree that most joint pain associated with AIs is mild to moderate and is best managed with analgesics. "Very few patients discontinue treatment because of arthralgia," the authors note.
More Findings
In the study, 120 postmenopausal patients with stage I to III breast cancer were evaluated for anatomic changes in the joints, and inflammatory markers were compared by Turkish investigators, led by Omer Dizdar, MD, from Hacettepe University Institute of Oncology in Ankara.
The team found that a range of markers of inflammation, such as C-reactive protein, were comparable in the patients taking AIs and the control subjects, and in the study participants with and without arthralgia.
The study supports previous reports that autoimmune disease "does not play a role in the etiology of AI-associated arthralgias," observes Dr. Chlebowski.
With regard to anatomic changes, the investigators found that the patients often had changes in their affected joints and tendons. Women taking AIs (n = 92) had increased tendon thicknesses, which is associated with the syndrome, compared with a control group of women (n = 28) with breast cancer not receiving the therapy (P < .01). Patients with AI-related arthralgia had more frequent joint and tendon effusions than those without pain (69% vs 42%; P < .05).
"These findings suggest that increased tendon thicknesses in patients on AIs may reflect some form of tendinopathy secondary to AI use. Further damage to the tendons and synovium results in effusions in tendon sheaths in a subgroup of patients, which is translated as arthralgia clinically," the authors write.
Anatomical matters aside, both Dr. Chlebowski and the study authors believe that arthralgia in this setting is also related to hormonal factors to some degree. Both note that joint pain is also a problem in postmenopausal women, even without breast cancer. In the landmark Women's Health Initiative (WHI) study, 74% of women without breast cancer reported joint pain, writes Dr. Chlebowski.
Notes on Managing Arthralgias
This study does not change the basic approach of clinicians to arthralgia, says Dr. Chlebowski.
At present, oncologists should carefully observe their patients for development of this problem.
"At present, oncologists should carefully observe their patients for development of this problem, clearly express to their patients the benefits of continued adherence [to AIs], and provide the limited available therapies," he writes.
The limited therapies can include acupuncture; 1 small pilot study suggested benefit from a 6-week regimen, notes Dr. Chlebowski. Vitamin D supplementation is a question "considered open," he adds, explaining that 2 ongoing studies are evaluating high-dose supplementation for AI-associated joint pain. However, 2 other trials, including the WHI, did not show any benefit from the vitamin, he says.
Joint pain associated with AIs still does not have an "optimal management strategy," writes Dr. Chlebowski.
Nevertheless, he cites a recent expert panel's recommendation to use "high-dose nonsteroidal anti-inflammatory drugs or selective COX-2 inhibitors as initial short-term therapy . . . to address initial pain relief, with subsequent titration to minimum effective dosage" (Ann Rheum Dis. 2007; 66:377-388).
Dr. Chlebowski reports being a consultant to AstraZeneca, Novartis, and Pfizer, all of which market AIs, and receiving honoraria from AstraZeneca and Novartis. The study authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print September 14, 2009. Abstract, Abstract
Metformin is more effective than chemotherapy alone - Study supports cancer stem cells hypothesis
In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in the September 14 online first edition of Cancer Research, a journal of the American Association for Cancer Research.
"We have found a compound selective for cancer stem cells" said lead researcher Kevin Struhl, Ph.D ., the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at Harvard Medical School. "What’s different is that ours is a first-line diabetes drug"
These findings add to a growing body of preliminary evidence in cells, mice and people that metformin may improve breast cancer outcomes in people. In this study, the diabetes drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.
The results fit within the cancer stem cell hypothesis, an intensely studied idea that small subsets of cancer cells have a special power to initiate tumors, fuel tumor growth and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor.
"There is a big desire to find drugs specific to cancer stem cells" said Struhl. "The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It’s already [in use as] a first-line diabetes drug"
The possible usefulness of a diabetes drug against cancer lends credence to an emerging idea that, in the vast and complex alphabet soup of molecular interactions within cells, a relatively few biological pathways will turn out to be most important for many different diseases, Struhl suggested.
In experiments led by postdoctoral fellows Heather Hirsch, Ph.D ., and Dimitrios Iliopoulos, Ph.D ., the combination of metformin and the cancer drug doxorubicin killed human cancer stem cells and non-stem cancer cells in culture. The researchers used four genetically distinct breast cancer cell lines.
In mice, pretreatment with metformin prevented the otherwise dramatic ability of human breast cancer stem cells to form tumors. In other mice where tumors took hold for 10 days, the combination therapy also reduced tumor mass more quickly and prevented relapse for longer than doxorubicin alone. In the two months between the end of treatment and the end of the experiment, tumors regrew in the mice treated with chemotherapy alone, but not in those who received both drugs. Metformin was ineffective in treating tumors when used alone.
"This is an exciting study" said Jennifer Ligibel, M.D ., a medical oncologist at the Dana-Farber Cancer Institute and a Harvard Medical School instructor in medicine. Ligibel and colleagues at the National Cancer Institute of Canada Clinical Trials Group are developing a large-scale phase II trial and will study its metformin’s impact on recurrence in women treated for early stage breast cancer.
"There is a lot of interest in studying metformin in breast cancer, but so far we do not have direct evidence that metformin will improve outcomes in patients" said Ligibel, who was not involved in the current study "That’s what this trial is for"
So far, observational studies have suggested a lower risk of cancers, including breast cancer, and better response to chemotherapy in patients with diabetes who are treated with metformin, she said. Results of basic science studies have also suggested plausible biological mechanisms. The study from the Struhl lab suggests a potential new pathway through which metformin could have an effect on breast cancer cells, according to Ligibel.
In their search for compounds that selectively destroy cancer stem cells, researchers hope to improve cancer outcomes. But the story is never as simple in human cancers, according to Kornelia Polyak, M.D ., Ph.D ., a breast cancer researcher at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School.
Cancer stem cells are a shifty target, said Polyak, who was not involved in the current study. For example, any cancer cell can acquire the properties of a cancer stem cell, and cancer stem cells can change into non-stem cancer cells, which can be just as deadly. Clinical trials in people are needed to test these ideas, according to Polyak.
The study by Struhl and colleagues is an offshoot of a larger project in his lab to systematically track how gene activity changes when cells transform into cancer. These changes were remarkably similar to gene dynamics in diabetes and other inflammatory conditions.
The researchers reasoned that if a common genetic pathway underlies different diseases, drugs that work against one disease might work against another. In a screen, the most effective drug inhibiting the transformation of cells into cancer was metformin, which led to the experiments in this study. They were further encouraged by the low dose of metformin needed for the effect in the laboratory, compared to the amount needed for analogous molecular experiments in basic diabetes research. The relative dosage for treating or preventing cancer is unknown and untested in people.
Struhl and Harvard Medical School have applied for a patent for a combined therapy of metformin and a lower dose of chemotherapy, which is being tested in animals. The National Institutes of Health and the American Cancer Society funded this research.
News Briefing: The American Association for Cancer Research will host a news briefing about the results of this study, which is published online first in Cancer Research.
Date: Monday, Sept. 14, 2009
Time: 10:00 a.m. ET
Panelists:
Moderator - Frank Rauscher, III, Ph.D.
Editor in Chief, Cancer Research
Professor, Gene Expression and Regulation Program
The Wistar Institute
Kevin Struhl, Ph.D.
David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
George Prendergast, Ph.D.
President, CEO and Professor
Lankenau Institute for Medical Research
Jennifer Ligibel, M.D.
Medical Oncologist
Dana-Farber Cancer Institute
FDA Questions Denosumab Safety in Advisory Meeting Documents
By John Gever, Senior Editor, MedPage Today
Published: August 11, 2009
FDA staff has expressed concerns that denosumab, the investigational biologic drug for osteoporosis, may increase risk of serious infections through its activity against an important immune system modulator.
The agency believes the drug -- provisionally trade-named Prolia -- could delay fracture healing as well. Some evidence suggests it could also promote tumor development and progression.
The concerns were revealed in briefing documents released in advance of a Thursday meeting of the agency's Advisory Committee for Reproductive Health Drugs, which will consider whether to recommend denosumab for approval.
Denosumab is a monoclonal antibody to RANKL, the receptor activator of nuclear factor-?B ligand. The molecule appears to help drive osteoclast development and activation, as well as playing a vital role in the body's defenses against infection.
If NF-?B is the immune system's "master switch," as it has been called -- controlling B- and T-cell differentiation and dendritic cell development -- then RANKL is the finger that flips the switch.
The drug's manufacturer, Amgen, filed last December for FDA approval of denosumab for preventing and treating osteoporosis in postmenopausal women, in women undergoing hormone ablation for breast cancer, and in men on androgen-deprivation therapy for prostate cancer.
Just this week, two of the registration trials for denosumab were published by the New England Journal of Medicine as early online releases. Those randomized, placebo-controlled studies showed that the drug was as effective as the best bisphosphonate drugs for osteoporosis.
The studies included more than 7,800 postmenopausal women with osteoporosis and close to 1,500 men with prostate cancer.
They also reported no indications of increased rates of serious infections, cancers, or most other serious adverse events, except for an increased incidence of eczema. (See Denosumab a Winner in Phase III Osteoporosis Trials)
The drug also boasts an extremely convenient dosing regimen -- subcutaneous injection every six months. Many clinicians believe this is a big advantage for denosumab, considering that compliance with daily oral medications for osteoporosis is notoriously poor.
But the drug's risk profile, especially with regard to infections and cancers in women being treated for postmenopausal osteoporosis, appears to be the FDA's chief concern going into the advisory committee meeting.
After pooling data from the clinical studies in postmenopausal osteoporosis submitted by Amgen (including phase I and II trials), agency staff found hints of potential problems.
"Overall, subjects in the denosumab group had a slightly increased incidence of serious infections," according to the briefing document. "There were more serious infections of the skin, ear, abdominal system and urinary tract. Also, endocarditis, infected arthritis and skin ulcers occurred more commonly in denosumab subjects. There were three denosumab subjects in phase I studies who developed pneumonia requiring hospitalization following a single dose of denosumab."
The document also noted that while Amgen did not perform carcinogenicity studies in animals because denosumab is not active in normal mice or rats, the clinical data showed a modest increase in certain malignancies in the human subjects.
"Three subjects receiving a high dose of denosumab in [a] dose-finding study died of a new malignancy," the staff review found. Those individuals received 100-mg doses, whereas 60 mg was used in the phase III studies and would likely be the recommended dose upon approval.
Pooled data from all the postmenopausal osteoporosis trials suggested "a slightly increased incidence" of breast, pancreatic, gastrointestinal, and reproductive-tract tumors.
Twice as many women discontinued denosumab versus placebo because of breast cancer, the reviewers noted -- 0.5% (20 cases) of patients receiving denosumab versus 0.3% (10 cases) of the placebo group.
Certain data also indicated that denosumab may produce unhealthy changes in bone structure, the review found.
According to the briefing document, both osteoclasts and osteoblasts were suppressed relative to patients taking placebo and alendronate. Markers of bone dynamics such as activation frequency, bone formation rates, and mineralizing surface were also much lower in denosumab-treated patients.
"This raises a concern that with long term use, suppression of bone remodeling may lead to complications such as delayed fracture healing, osteonecrosis of the jaw, or atypical fracture," the document said.
Neither of the two New England Journal of Medicine reports this week, however, gave any indication of clinical bone problems associated with denosumab. Authors of those studies said they found no signs of delayed bone healing after fracture and there were no cases of jaw osteonecrosis, a rare but frightening side effect of bisphosphonate drugs.
The FDA document confirmed that no actual cases of jaw osteonecrosis were seen in any of the osteoporosis or hormone ablation trials.
But one case was reported in another trial sponsored by Amgen in patients with multiple myeloma and metastatic cancer.
Also, the clinical data alleviated concerns about possible adverse cardiovascular events, such as promotion of atherosclerosis, that were hypothesized on the basis of its anti-RANKL mechanism.
And, deaths were no more frequent in denosumab groups versus placebo in the trials.
In light of the safety worries that still remain with the drug, the advisory committee will be asked to comment on whether a risk evaluation and mitigation strategy should be required as a condition of denosumab's approval.
The agency is not bound to follow its advisory committee's recommendations, but it usually does.
Extreme Diet and Breast Cancer Risk
UK researchers observing a small group of women who followed an extreme 900 calorie a day diet found they had reduced expression of a cancer growth gene and changes in blood biomarkers for breast cancer. If these findings are confirmed in larger trials, the researchers hope they will help experts recommend specific diet changes to women at higher risk of breast cancer so they can reduce their likelihood of developing the disease.
The study was conducted by Professor Anthony Howell, Director of the Breakthrough Breast Cancer Research Unit at The University of Manchester, and his team, and was published online on 1 August in the journal Cancer Prevention Research.
Previous studies have already shown that calorie restriction, more formally termed Dietary Energy Restriction (DER), reduces the risk of spontaneous breast cancer in rats and mice, and in women who follow DER before the menopause it seems to reduce the risk of getting breast cancer after the menopause.
However, what is missing from the science is reliable markers of DER so that robust DER regimens for preventing breast cancer can be designed. So Howell and colleagues set out to investigate some DER biomarkers in breast and fat tissue and blood (serum).
For the study they recruited 19 women aged between 35 and 45 who were either overweight or obese and assessed to be at moderate risk of developing breast cancer due to family history (their lifetime risk ranged from 1 in 6 to 1 in 3).
The women were randomly assigned either to follow a DER regimen (10 participants) or continue a normal eating pattern (9 participants) of about 2,000 calories a day for one menstrual cycle.
Before and after the trial, the women underwent biopsies of breast and belly fat tissue and also gave blood and urine samples.
To look at genetic changes, Howell and colleagues extracted RNA from whole tissues and breast epithelium. To look for biomarkers, the blood and urine sample were used to generate metabolic profiles.
The results showed that:
• Not surprisingly, DER was linked to significant reductions in weight.
•
• DER was also linked to changes in serum biomarkers of breast cancer risk, including insulin, leptin (a hormonal biomarker for body fat), total and low-density ("bad") lipoprotein cholesterol, and triglycerides (high levels of these are often linked to higher risk of a range of diseases).
•
• In both breast tissue, belly tissue, and some isolated breast epithelial cells, there was evidence that genes involved in key metabolic pathways for fats and other substances (glycolytic and lipid pathways) were less active ("significantly down-regulated").
•
• This included a reduction in the expression of Stearoyl-CoA desaturase (SCD), a gene linked to cancer growth. This is the first time this has been observed in breast tissue.
Howell and colleagues concluded that:
"Reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents."
Howell told the media that he and his team wanted to thank the women who took part in the trial:
"The women who took part in this study made a major commitment to help us carry out this vital research."
"They enabled us to look for the first time at changes that occur within the breast tissue that may make cancer growth less likely. These results will now need to be tested in larger groups of women over longer periods of time," he added.
Dr Alexis Willett, Head of Policy at the UK charity Breakthrough Breast Cancer, said:
"We already know that the more weight a woman gains over the course of her adult life, the higher her risk of developing breast cancer will be after she has gone through the menopause. However, it is important to find out more about how lifestyle changes like losing weight can affect breast cancer risk."
"We wouldn't advise women to follow a diet of this kind as those who took part were closely monitored by a specialist dietician. We recommend that women maintain a healthy weight to reduce their breast cancer risk," added Willett.
Salinomycin Attacks Stem Cells in Breast Cancer
In tests in mice, salinomycin killed breast cancer stem cells far more effectively than some existing drugs, and slowed tumour growth.
The drug, a farm antibiotic, has yet to be tested in humans, the journal Cell reports.
But UK experts warned a human version could be some years away.
The reasons why, even following powerful chemotherapy, some cancers can grow back, are not fully understood.
Many scientists believe a key role lies with stem cells, which can be resistant to conventional chemotherapy, remaining to 'seed' new tumours and drive their growth.
The drug's potential was identified by researchers at the Massachusetts Institute of Technology, who tested 16,000 existing chemical compounds against breast cancer stem cells in the laboratory.
Those which performed the best were then tried in mice, and compared to existing drugs such as paclitaxel.
Salinomycin appeared to be 100 times better at killing the cells in a test tube, and treated cells were much less likely to start new tumours when injected into mice.
When given to mice with tumours, the growth of the cancer slowed.
However, the researchers stressed that it was too early to know if similar successes could be achieved in human cancer patients.
"Many therapies kill the bulk of a tumour only to see it regrow," said Professor Eric Lander, from MIT."This raises the prospect of new kinds of anti-cancer therapies."
'Very early research'
Dr John Stingl, group leader in mammary stem cell biology at Cancer Research UK's Cambridge Research Institute, said: "This is one of the biggest advances we have seen this year in this area of research. These scientists have demonstrated that it's possible to selectively target the rare cancer stem cells that drive tumour growth.
"This research also introduces a completely new way of identifying cancer drugs. The challenge for the future is to bring this class of drugs to the clinic and to identify the patients that are likely to respond to them."
Dr Alexis Willett, head of policy at Breakthrough Breast Cancer, added: "There is evidence that stem cells may enable breast cancers to form and grow.
"This research provides a clue as how to identify these cells and how they might be targeted and destroyed. "It's important to remember that this is very early research and it will be some time before it is clear whether this leads to an effective breast cancer treatment."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/8201376.stm
"Biomarkers of Dietary Energy Restriction in Women at Increased Risk of Breast Cancer."
Ong, Kai Ren, Sims, Andrew H., Harvie, Michelle, Chapman, Mary, Dunn, Warwick B., Broadhurst, David, Goodacre, Royston, Wilson, Mary, Thomas, Nicola, Clarke, Robert B., Howell, Anthony.
Cancer Prev Res 2009 2: 720-731.
Published online, August 1, 2009.
DOI: 10.1158/1940-6207.CAPR-09-0008
Sources: Manchester University.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Ovary Removal Linked to Increased Lung Cancer Risk
New York Times
By RONI CARYN RABIN
Women who undergo hysterectomies often have both ovaries removed along with the uterus in order to prevent ovarian cancer. But a new study suggests ovary removal may increase the risk of another seemingly unrelated ailment, lung cancer.
University of Montreal scientists stumbled onto the connection while investigating the relationship between lung cancer and hormones in women. They found no relationship between hormonal factors like menstruation patterns, child-bearing or breast-feeding histories and the risk of lung cancer. The researchers did, however, discover that women whose menopause had been induced medically were at 1.92 times greater risk of developing lung cancer than women who had experienced natural menopause.
“We were surprised — we had no prior expectation of this finding,” said Anita Koushik, a researcher at the University of Montreal’s Department of Social and Preventive Medicine and the first author of the study, published online in May in The International Journal of Cancer. “Aside from the fact that smoking increases your risk of lung cancer, the results of this study suggest that having a non-natural menopause contributes to an almost doubling of the risk.” She noted, though, that the findings could have occurred by chance.
The vast majority of women who had experienced a non-natural menopause had had both ovaries surgically removed, she added.
While smoking is the leading cause of lung cancer, other factors may play a role in enhancing the impact of the carcinogens in tobacco, Dr. Koushik said. In women, these factors could be hormonal. Both normal and cancerous lung tissue express estrogen receptors and may be influenced by levels of the hormone in the body, Dr. Koushik said. The patterns of expression are different in men and in women.
Medically induced menopause usually occurs at a younger age than natural menopause. Surgical menopause results in a sudden drop in estrogen levels, compared with the more gradual decline in hormone levels that occurs with natural menopause. Dr. Koushik suggested the increased lung cancer risk may be linked to the impact of plummeting hormone levels.
In the study, the scientists examined data on 422 women diagnosed with lung cancer in the greater Montreal area in 1996 and 1997 and compared them with 577 randomly selected control subjects. The women were asked about a variety of hormone-related factors, including when they got their first periods, how many children they had, whether they breast-fed their children and whether they had gone through menopause. The researchers also gathered detailed information about smoking, occupational history, education and family income.
The report is not the first to link ovary removal with an increased risk of lung cancer. A recent analysis of data from the Nurses’ Health Study, published in the journal Obstetrics and Gynecology in May, reported that women who had had hysterectomies but kept their ovaries lived longer than women who had had the procedure but whose ovaries were removed.
While those who had their ovaries removed were less likely to develop breast cancer and virtually eliminated their risk of ovarian cancer, they were more prone to heart disease and were at greater risk for other kinds of cancer, including a doubling of the risk for lung cancer among those women who never used hormone therapy.
(See 2009 SABCS Report on how Aromatase Inhibitors reduce lung cancer risk)
Blood Pressure Drug Blocks Newly Found Breast Cancer Gene
Blood Pressure Drug Losartan Shrinks Cancer Tumors by 30% in Study
By Gina Shaw
WebMD Health News
Reviewed by Louise Chang, MD
June 1, 2009 -- Researchers at the University of Michigan have identified a gene that may be involved in as many as one in five breast cancers. And the gene could be blocked by a common blood pressure drug.
The gene, AGTR1, caused normal breast cells to act like highly invasive cancer cells, both in the laboratory and in mice. When the mice were then treated with an FDA-approved blood pressure drug, losartan, tumors that overexpressed AGTR1 shrunk by 30% within eight weeks.
The Hunt for Breast Cancer Genes
The researchers identified AGTR1 by using gene expression profiling data to compare thousands of genes that might be linked to breast cancer. AGTR1 was overexpressed (or overly productive of its gene product) in 10% to 20% of all breast cancers -- second only to HER2, which is found in 25% to 30% of all breast cancers and responds well to the drug Herceptin.
“HER2 ... makes breast cells cancer-like. That’s very similar to what we found with AGTR1,” says Daniel Rhodes, PhD, a research investigator in the Michigan Center for Translational Pathology and the lead author of the study, which appears in the June 1 edition of Proceedings of the National Academy of Sciences. Rhodes is also the founder and CEO of a cancer genomics company, Compendia Biosciences.
Breast cancer researchers have been looking for other targets similar to HER2 in order to develop more targeted treatments for women whose breast cancers are not HER2-positive and therefore do not respond to Herecptin.
Blood Pressure Drugs for Breast Cancer
Because AGTR1 is involved in the constriction of blood vessels, its activity is blocked by a class of drugs called angiotensin receptor blockers, which include losartan, the drug tested in this study. “This is particularly exciting, because losartan is such a safe and widely prescribed therapy,” Rhodes says. “This makes it much easier to do a clinical trial.”
If losartan really does block the cancer-promoting activity of AGTR1, why hasn’t anyone identified a lower rate of breast cancer among women taking the drug for high blood pressure?
“One would expect epidemiologic studies to show a reduction in BC [breast cancer] risk in people taking this drug,” says Clifford Hudis, MD, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York. “I don’t remember ever seeing hypertension and treatment for hypertension as indicators of lower breast cancer risk. We have lots of patients who get treated for breast cancer and take anti-hypertensives, so you would expect to see that pop out as an indicator of good outcomes.”
But not all high blood pressure drugs specifically block the AGTR1 receptor. “We think that true blockers to the AGTR1 protein would have the strongest effect, and these drugs, like losartan, are generally used as second-line therapies for hypertension,” Rhodes tells WebMD. "If only a few women in 100 are being treated with angiotensin receptor blockers, and only 10% to 20% of all breast cancers are AGTR1-positive, you’d need thousands of patients to see an effect.”
Developing a Test for AGTR1-Positive Tumors
But if there were a study in which losartan were given only to women with breast cancers linked to overexpression of AGTR1, it would be much easier to detect an effect. Before such a trial can be set up, however, scientists must first develop a way to easily detect AGTR1 overexpression.
Once that test is available -- something that should take only a few months, says Rhodes -- a clinical trial should be easier than usual to set up because of the availability of an existing, approved therapy whose side effects are known. “No trial is specifically planned yet, but we are talking with our clinical colleagues about it and there is a great deal of interest,” he says.
“If the data can be confirmed, it’s not a big stretch to imagine setting up a randomized study relatively easily,” Hudis says. “I definitely think this should be investigated further, although as always when we don’t yet have data in humans, you have to be careful and not jump to conclusions.”
The University of Michigan has filed a patent on AGTR1 and is seeking commercial partners.
New report states that breast ultra sounds are 100% accurate. Read on to see how misleading this is.
A new report has been released today to tell us all that breast ultrasounds pick up tumors 100% of the time in women under 40.
Really?
My tumor, which was found when I was in my 30s, was picked up on mammogram and when the docs did a follow-up ultrasound it was not there. The radiologist said that since it was not picked up on both, I should "watch and wait" for six months.... Fortunately I have a gyn who hates cancer as much as I do and he insisted on an immediate biopsy. That resulted in finding a grade 3, highly aggressive Triple Negative Breast Cancer next to my chest wall. If I had followed the three most dangerous words in the English language, "watch and wait" my TN tumor would have made a nice, comfy home for itself in the chest wall and the vascular and lymphatic system. Would I still be here? I don't know- Ferne isn't... and she was told to wait.
Here is the article- tell your friends to not take this as gospel because it could be deadly. The TRUTH IS: Women under 40 need better screening. It is NOT just replacing mammography with ultrasounds. If they really gave a damn about us they would find a way to get EVERYONE Breast MRIs which can find tumors as small as 7mms. But who is going to pay for that? We have research into erectile dysfunction to fund.... the Space Shuttle to launch to change the spark plugs on the International Space Station.... Think about it.
CHICAGO (Reuters) - Breast ultrasounds found 100 percent of suspicious cancers in women under 40 who found lumps or other suspicious areas of the breast, offering a cheaper, less-invasive alternative to surgery or biopsies, U.S. researchers said on Wednesday.
They said targeted ultrasound -- which examines just the area of the breast where a lump is identified -- should become the standard of care for women under 40.
The findings may address some of the concerns raised by a federal advisory panel about breast exams done by women or doctors to investigate lumps or hot spots in the breast, which most often turn out to be harmless.
In a controversial set of recommendations issued last month, the U.S. Preventive Services Task Force recommended that women not be taught to perform self breast exams because they often result in worry and expense for tests, biopsies and unnecessary surgery.
"That concerns us because while breast cancer in young women is rare, it absolutely does occur. Often, those cancers are only diagnosed because the woman noticed the lump in her breast or her doctor noticed a lump in her breast," said Dr. Constance Lehman of the University of Washington and director of imaging at the Seattle Cancer Care Alliance, who presented her findings at the Radiological Society of America meeting in Chicago.
"There are harms that follow after a woman does a self breast exam -- unnecessary surgeries, unnecessary biopsies. To that point, what we're saying is if you use imaging appropriately you can avoid those harms," Lehman said in a telephone interview.
Lehman did two studies testing the effectiveness of ultrasound to distinguish between potentially cancerous lumps and harmless masses in younger women.
In one, they studied more than 1,100 ultrasound exams of women under age 30. In the second, they studied 1,500 exams in women aged 30 to 39.
In both studies, ultrasound correctly identified the cancers and all of the benign breast changes. The only cancer not found was in a region of the breast that was not identified as an area of concern. Instead, it was identified by a full breast mammogram.
"Less than 3 percent of the patients that presented in this way had cancer. But it's important for us to find those patients that did have cancer," Lehman said.
"We had 26 women whose cancers were diagnosed because they brought the lump to the attention of their doctor, or their doctor brought the lump to the attention of the breast imaging specialist," she said.
Lehman said in the United States there is no standard way of treating women under age 40 who find a lump in their breast.
"Some of them go to the operating room to have the lump removed. Others have it followed. Others have a needle biopsy and we wanted to bring some clarity to this treatment," she said.
She said ultrasound is a quick and easy test that uses sound waves to create an image of the breast. It typically costs $100 to $200 per exam.
Lehman said using ultrasound could help balance some of the harms of overtreatment with the benefits of self breast exams in women under age 40, who are too young for routine mammogram screening even under the American Cancer Society guidelines.
The task force also recommended against routine mammogram screening for women in their 40s for many of the same reasons, a change the American Cancer Society and many other breast cancer experts reject.
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