2011 SAN ANTONIO BREAST CANCER SYMPOSIUM NEWS ROUNDUP
December 7, 2011
Today's abstracts reaffirm the benefits of using Zometa with endocrine therapy to prevent recurrence. There is now a test for recurrence risk in DCIS patients. The poor prognosis of overweight women is further studied. And, directly in line with our Before Forty Initiative, Hispanic women are diagnosed younger than non-hispanics and are more likely to develop a very aggressive, non-responsive form of Triple Negative Breast Cancer. They have a high mortality rate. Imagine if our Before Forty Initiative was able to help these women? We are working hard to do just that. Abstracts below. More to follow tomorrow.
Immediate Bisphosphonate Use With Endocrine Therapy Reduced
Recurrence, Increased Survival in Postmenopausal Early Breast Cancer
• Long-term data confirm overall survival benefit with zoledronic acid.
• Women five years postmenopause had greatest benefit.
• Even delayed use of zoledronic acid reduced recurrence vs. no use.
SAN ANTONIO — The addition of zoledronic acid to adjuvant endocrine therapy
increased bone mineral density and reduced the risk for disease recurrence among
postmenopausal women with early hormone receptor-positive breast cancer, according to
new data from the ZO-FAST trial.
Richard de Boer, M.D., of the Royal Melbourne Hospital in Victoria, Australia, presented
long-term data from the Zometa-Femara Adjuvant Synergy Trial (ZO-FAST) at the
2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.
De Boer and colleagues explored adding zoledronic acid, an intravenous bisphosphonate,
to adjuvant endocrine therapy to reduce bone mineral density loss seen with aromatase
inhibitors and to improve survival outcomes.
When he presented initial data from ZO-FAST at the 2010 CTRC-AACR San Antonio
Breast Cancer Symposium, de Boer indicated that early zoledronic acid resulted in a
significantly improved bone mineral density and an improved disease-free survival. At
this year’s symposium, he reported long-term data and data on the effect of menopausal
status at breast cancer diagnosis on disease-free survival.
Researchers randomly assigned 1,065 patients who were about to commence letrozole, an
aromatase inhibitor, to receive immediate zoledronic acid every six months or to a
delayed group where zoledronic acid was started at a later time only if the patient
experienced a fracture or a documented fall in bone mineral density.
Immediate Bisphosphonate Use With Endocrine Therapy Reduced Recurrence,
Increased Survival in Postmenopausal Early Breast Cancer
Page 2 of 2
After 60 months of follow-up, “the primary endpoint of the trial was successfully
achieved — up-front zoledronic acid significantly decreased bone mineral density loss in
both the lumbar spine and the hip,” de Boer said. “The secondary endpoint of an
improvement in disease-free survival was also met with a 34 percent decrease in disease
recurrence in the patients receiving the up-front zoledronic acid.”
Researchers conducted an exploratory subgroup analysis based on menopausal status at
the time of breast cancer diagnosis. Data indicated that in women who were truly
menopausal at diagnosis, immediate treatment with zoledronic acid reduced the risk for
disease recurrence by 29 percent and improved overall survival by 35 percent.
“In addition, patients in the delayed group, who did not start with zoledronic acid but
who switched to start at a later time, also appeared to benefit from the zoledronic acid
with an improvement in disease outcomes compared with those women who never started
the bisphosphonate,” de Boer said.
Additional studies are needed to fully define the patient populations most likely to benefit
from adjuvant zoledronic acid in this setting.
Until then, “patients with hormone receptor-positive breast cancer who are
postmenopausal and about to commence letrozole have the option of considering the
addition of zoledronic acid — primarily to maintain bone mineral density but also with
the aim of reducing the risk for disease recurrence,” de Boer said.
# # #
Presenter: Richard de Boer, M.D.
Abstract Number: S1-3
Title: Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-
Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year
Follow-Up of ZO-FAST.
Author Block: R de Boer1, N Bundred2, H Eidtmann3, P Neven4, G von Minckwitz5, N Martin6,
A Modi6 and R Coleman7. 1Royal Melbourne Hospital, Victoria, Australia; 2University Hospital
of South Manchester NHS Foundation Trust, Manchester, United Kingdom; 3University
Frauenklinik, Kiel, Germany; 4Breast Clinic, UZ Gasthuisberg, Leuven, Belgium; 5German
Breast Group, Frankfurt, Germany; 6Novartis Oncology, East Hanover, NJ and 7University of
Sheffield, Sheffield, United Kingdom.
Introduction: Recent clinical trials suggest potential anticancer activity for bisphosphonates
combined with adjuvant endocrine therapy in patients with hormone receptor-positive (HR+)
early breast cancer (EBC). Data from the interim analysis of AZURE suggest that the benefits of
adding zoledronic acid (ZOL) may be greatest in patients with low estrogen levels (Coleman RE,
et al. SABCS 2010). In ZO-FAST, we have previously demonstrated that adding ZOL to
adjuvant therapy significantly improved bone mineral density (BMD) and prolonged disease-free
survival (DFS) vs delayed ZOL (de Boer R, et al. SABCS 2010). We report here the effect of
time since menopause at breast cancer diagnosis (ie, baseline menopausal status) on DFS
benefits with ZOL.
Methods: Postmenopausal women with HR+ EBC receiving letrozole (LET; 2.5 mg qd × 5 yr)
with a BMD T-score ≥–2 (N=1065) were randomized to ZOL (4 mg q6mo): immediate (IMZOL)
or delayed (DZOL; initiated for postbaseline T-score <–2 or nontraumatic/asymptomatic
fracture). Patients were followed for disease recurrence and overall survival (OS) for 5 years.
Patients were eligible for the study if they had established menopause at the time of diagnosis, or
if they became menopausal because of chemotherapy or ovarian suppression (ie, recently
postmenopausal). The effect of baseline menopausal status on DFS was examined in Cox
regression analyses.
Results: At 60 months' follow-up in the overall population (N=1065), IMZOL significantly
reduced the risk of a DFS event by 34% vs DZOL (hazard ratio [HR]=0.66; 95% confidence
interval [CI], 0.44-0.97; P=.034). In exploratory analyses of women who were postmenopausal
for >5 years or >60 years old at study entry (n=670), IMZOL improved DFS (HR=0.63; 95% CI,
0.39-1.01; P=.052) and significantly prolonged OS (HR=0.50; 95% CI, 0.27-0.92; P=.022) vs
DZOL. Additional subgroup analyses including patterns of breast cancer recurrence will be
presented. During 5 years of treatment, osteonecrosis of the jaw (ONJ) was reported in 4/669
patients (0.6%) who received ZOL, and there was no increase in renal adverse events (AEs) in
the ZOL-treated patients. Overall, AEs were consistent with the known safety profiles of both
study drugs.
Conclusions: Long-term follow-up in ZO-FAST confirms the overall survival benefits of adding
ZOL (4 mg q6mo) to adjuvant LET therapy for EBC. However, subset analyses suggest that
women with established postmenopausal status may benefit from ZOL therapy more than others.
These results are consistent with observations in the AZURE trial, and support potentially greater
ZOL benefits in a low-estrogen environment. Additional studies are needed to fully define the
patient populations most likely to benefit from adjuvant ZOL in this setting.
###
New Test Predicts Risk for Recurrence for
Patients With DCIS
• Multigene assay predicts risk for local recurrence for patients with DCIS.
• This advance combines knowledge of the genome and new molecular
technologies.
• Test allows physicians to individualize treatment so that lower-risk patients
avoid radiation.
SAN ANTONIO — In a significant advance for patients with ductal carcinoma in situ,
researchers have developed and prospectively validated a multigene test to identify the
risk for recurrence of breast cancer.
The method combines measuring tumor gene expression with a gene expression
algorithm to decipher the genetic underpinnings of a patient’s cancer and determine
whether the individual patient should be treated with surgery (usually lumpectomy) or a
combination of surgery and radiation.
This is the first time a multigene test has been used to differentiate lower-risk and more
aggressive forms of ductal carcinoma in situ (DCIS) and will allow physicians to spare
many patients the need to undergo radiation, according to researchers.
Lawrence J. Solin, M.D., FACR, FASTRO, chair of the department of radiation oncology
at Einstein Medical Center in Philadelphia, presented the results at the 2011 CTRC-
AACR San Antonio Breast Cancer Symposium (SABCS), held Dec. 6-10, 2011.
“Using a molecular-based assay, we have successfully identified patients at higher risk
for recurrence and patients at lower risk,” said Solin. “This is an important advance for
women with newly diagnosed DCIS. By predicting individual risk, physicians can
provide a more tailored treatment program for each patient.”
The validation study of the DCIS Score was a collaboration among the Eastern
Cooperative Oncology Group (ECOG), North Central Cancer Treatment Group and
Genomic Health. The validation utilized patient tumor samples from E5194, an ECOG-
led, multi-institutional study of patients with low-, intermediate- or high-grade DCIS who
had been treated surgically but had not received radiation. E5194 was the first
prospective study of local excision alone for DCIS, and its five-year results were reported
at SABCS in 2006 (L. Hughes).
Researchers tested and scored tumors from 327 patients to determine their risk for
recurrence. The DCIS validation study team used the Oncotype DX breast cancer assay,
which has been available for invasive breast cancer since 2004, and a DCIS Score
algorithm to study these tumor samples.
The test uses reverse transcriptase-polymerase chain reaction technology, which
quantitates the level of RNA in the individual tumor sample to reveal its underlying
biology. The level of RNA is then used by a prespecified algorithm to calculate a DCIS
Score, which predicts the likelihood of local recurrence, defined as either the
development of a new invasive breast cancer or the recurrence of DCIS.
Solin also reported 10-year results of E5194, in which 46 patients had an ipsilateral breast
event (IBE; defined as ipsilateral local recurrence of DCIS or invasive cancer) at a
median follow-up of 8.8 years. Continuous DCIS Score was significantly associated with
IBE when adjusted for tamoxifen use and provided value beyond the traditional measures
of tumor size, tumor grade and margin status.
Numerous studies, including the current study, have shown that routine, microscopic
pathology grading is not a reliable indicator of the risk for recurrence.
“The DCIS Score will help physicians understand the underlying biology of DCIS for an
individual patient and accurately gauge the risk for that person,” said Solin. “As a result,
the patient and physician can decide on the appropriate course of treatment based on a
more complete understanding of the risk involved.”
# # #
Presenter: Lawrence J. Solin, MD, FACR, FASTRO
Abstract Number: S4-6
Title: A Quantitative Multigene RT-PCR Assay for Predicting Recurrence Risk after Surgical
Excision Alone without Irradiation for Ductal Carcinoma In Situ (DCIS): A Prospective
Validation Study of the DCIS Score from ECOG E5194.
Author Block: Lawrence J Solin1, Robert Gray2, Frederick L Baehner3, Steven Butler3, Sunil
Badve4, Carl Yoshizawa3, Steven Shak3, Lorie Hughes5, George Sledge6, Nancy Davidson7, Edith
A Perez8, James Ingle9, Joseph A Sparano10 and William Wood11. 1Radiation Oncology, Albert
Einstein Medical Center, Philadelphia, PA; 2Eastern Cooperative Oncology Group, Boston, MA;
Genomic Health, Inc., Redwood City, CA; 4Pathology, Indiana University, Indianapolis, IN;
North Georgia Radiation Therapy, The Hope Center, Cartersville, GA; 6Medical Oncology,
Indiana University, Indianapolis, IN; 7Medical Oncology, University of Pittsburgh, Pittsburgh,
PA; 8Medical Oncology, Mayo Clinic Jacksonville, Jacksonville, FL; 9Medical Oncology, Mayo
Clinic Rochester, Rochester, MN; 10Medical Oncology, Albert Einstein College of Medicine,
Bronx, NY and 11Surgery, Emory University, Atlanta, GA.
Background: We have previously reported the results of surgical excision without irradiation for
selected patients with DCIS in ECOG E5194, where the 5-year rates of local recurrence varied
with age, grade, and lesion size (Hughes et al. J Clin Oncol 27:5319, 2009). New methods are
needed to provide more accurate and reproducible assessment of recurrence risk.
Methods: ECOG E5194 included 670 eligible patients with DCIS treated with surgical excision
(≥ 3 mm negative margins) without irradiation, 228 of whom received tamoxifen. Patients had
low or intermediate grade DCIS ≤ 2.5 cm, or high grade DCIS ≤ 1 cm. The Oncotype DXR assay
was performed by quantitative RT-PCR using formalin fixed paraffin embedded tumor
specimens from 327 patients (49% of the parent study). Recurrence ScoreR (RS) was calculated
using the published algorithm. A new, prespecified DCIS Score™ was designed to predict
recurrence using an optimized gene expression algorithm. The primary objective was to
determine whether there was a significant association between the risk of an ipsilateral breast
event (IBE) and the continuous DCIS Score in Cox models. 46 patients had an IBE (defined as
ipsilateral local recurrence of DCIS [n=20] or invasive cancer [n=26]). Median follow-up was
8.8 years.
Results: The 10-year IBE rates were 15.4% for low/intermediate grade DCIS and 15.1% for
high-grade DCIS (as determined by central pathology review), and for invasive IBE, 5.6% and
9.8%, respectively. Comparison between local and expert grading showed substantial
disagreement. Continuous DCIS Score was significantly associated with IBE (HR 2.34 per 50
units; 95% CI 1.15, 4.59; p=0.02) when adjusted for tamoxifen use (prespecified primary
analysis) and with invasive IBE (HR 3.73; CI 1.34, 9.82; p=0.01). DCIS Score was significantly
associated with outcome when evaluated by the prespecified risk groups (see Table). Similar
results were observed with and without adjustment for tamoxifen use or for negative margin
width. Features associated with IBE in multivariate models included menopausal status (HR
0.49; 95% CI 0.27, 0.90; p=0.02), tumor size (HR 1.52 per 5 mm; 95% CI 1.11, 2.01; p=0.01),
and continuous DCIS Score (HR 2.41; 95% CI 1.15, 4.89; p=0.02). The standard RS, which is
calculated using thresholding of many genes unlike the DCIS Score, was not associated with IBE
or invasive IBE (p > 0.6).
Conclusions: We have prospectively validated a multigene assay that quantifies recurrence risk
and complements traditional clinical and pathologic factors in selected patients with DCIS
treated with surgical excision without irradiation. The DCIS Score provides a new clinical tool
for individualized selection of treatment for patients with DCIS.
Breast Cancer Mortality Higher in Hispanic Women
Hispanic women had a 20 percent increased risk for death from breast
cancer. Tumor-related factors may primarily account for this difference.
Hispanic women may be more likely to have a tumor phenotype resistant to
chemotherapy.
SAN ANTONIO — Hispanic women are more likely to die from breast cancer than non-
Hispanic white women, according to research presented at the 2011 CTRC-AACR San
Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.
“This difference may be associated with a tumor phenotype that is less responsive to
chemotherapy,” said Kathy B. Baumgartner, Ph.D., professor of epidemiology and
associate dean for faculty affairs in the School of Public Health and Information Sciences
at the University of Louisville in Kentucky. “Increased awareness of this ethnic disparity
is needed to improve survival in Hispanic women with breast cancer.”
Breast cancer is the most common cancer and is the second cause of cancer death in
women in the United States. Incidence and survival rates vary by ethnicity, and previous
research has demonstrated a trend toward poorer survival in Hispanic women.
From 1992 to 1996, Baumgartner and colleagues conducted the New Mexico Women’s
Health Study (NMWHS), a statewide, population-based, case-control breast cancer study
that examined the difference between Hispanic and non-Hispanic white women for breast
cancer risk. In all, 692 women with a first primary breast cancer participated.
In a recent study, researchers followed the 577 women with invasive breast cancer
through 2008 to assess differences in long-term survival between Hispanic and non-
Hispanic white women in the NMWHS.
Hispanic women were about 20 percent more likely to die from breast cancer than non-
Hispanic white women, which is consistent with other reports, Baumgartner said. After
adjusting for age, stage, lymph node involvement and estrogen receptor (ER) status, the
researchers saw the risk drop considerably to almost equal that of non-Hispanic white
women — suggesting that “the ethnic difference in breast cancer mortality may be mostly
biologically based,” Baumgartner said.
In addition, Hispanic women who received chemotherapy were about 1.5 times more
likely to die from breast cancer compared with non-Hispanic white women who received
chemotherapy, after adjusting for age and the characteristics noted above.
“It is not clear how much of this ethnic difference in survival is due to socioeconomic
factors influencing access to screening and treatment or to biological ones,” Baumgartner
said. “Some studies suggest that Hispanic women are more likely to develop ER-negative
tumors that are resistant to chemotherapy.”
She added, “Altered response to chemotherapy may partly explain the Hispanic vs. non-
Hispanic white disparity in breast cancer survival.”
There was no difference between Hispanic and non-Hispanic white women for all-cause
or non-breast cancer mortality.
Baumgartner and her colleagues will continue to monitor this cohort for the long term.
This research was supported by a grant from the National Cancer Institute and the James
Graham Brown Cancer Center.
# # #
Presenter: Kathy B. Baumgartner, Ph.D.
Abstract Number: P1-08-28
Title: Differences in long-term survival for Hispanic and non-Hispanic white women with breast
cancer.
Author Block: Kathy B Baumgartner1, Christina M Pinkston2, Stephanie R Denkhoff3 and
Richard N Baumgartner4. 1Epidemiology & Population Health, School of Public Health &
Information Sciences, University of Louisville, Louisville, KY, United States; 2Epidemiology &
Population Health, School of Public Health & Information Sciences, University of Louisville,
Louisville, KY, United States; 3Epidemiology & Population Health, School of Public Health &
Information Sciences, University of Louisville, Louisville, KY, United States and 4Epidemiology
& Population Health, School of Public Health & Information Sciences, University of Louisville,
Louisville, KY, United States.
Body: Trends towards poorer survival in Hispanic (H) women have been previously reported, but these studies are limited by small sample sizes or lack of sufficient covariate data. Overall, H women are more likely to be diagnosed with breast cancer at a younger age, with hormone receptor negative tumors, with more advanced stage at diagnosis, and with worse prognosis.
Data are limited on survival experience for H women, leading to unanswered questions and concerns, as this ethnic group is a rapidly growing fraction of the U.S. population. Although survival can be evaluated based on national data, important covariates are lacking. The analyses for this study focus on survival differences between H and non-Hispanic white (NHW) women and factors associated with this difference.
Previous reports suggest that breast cancer survival is significantly worse in H compared to NHW women, even with adjustment for age, stage, histology, and treatment. The New Mexico Women's Health Study (NMWHS) was a statewide population-based, case-control breast cancer study that included 1,566 H and NHW women conducted from 1992-1996. It was designed to investigate etiologic risk factors associated with the difference in breast cancer incidence between H and NHW women. Women diagnosed with a new primary in situ or invasive breast cancer were ascertained through the New Mexico Tumor Registry (NMTR) and eligibility was based on the following criteria: age 20-74 years, diagnosis year 1992-1994, and New Mexico residence at diagnosis. All identified H cases and approximately 33% of identified NHW cases comparable to the age and geographic distribution of H cases were eligible for the study.
Of the 984 eligible cases identified, 73% completed an interview: 339 H (69%); 388 NHW (78%). The National Death Index (NDI) was used to determine vital status through December 31, 2008, the most recent date for which NDI data are available. Data for clinical and tumor characteristics were obtained through linkage with the NMTR. The respective crude hazard ratios (HR) for all-cause, breast cancer-specific, and non breast cancer mortality over the 14-year follow-up period for H women compared with NHW women were 1.09 (95%CI 0.84-1.42), 1.29 (0.91-1.84), and 0.88 (0.59-1.31), respectively.
These results suggest that breast cancer-specific mortality, is increased in H relative to NHW women, while there is no ethnic difference in all-cause or non-breast cancer mortality. Restriction of the analysis for breast cancer mortality to cases with invasive cancer (n=692) did not meaningfully alter the crude HR for H women (HR=1.24, 95%CI 0.84-1.74). Evaluation of breast cancer mortality by ethnicity and chemotherapy treatment, adjusting for stage of disease, lymph node and estrogen receptor status suggested that H women receiving chemotherapy have worse survival (p=0.052 for statistical interaction), which may be due to factors such as altered
response to chemotherapy or possibly poor compliance.
###
Obesity Linked to Worse Outcomes in Early Breast Cancer Treatment
• In the overall group, obese patients had an increased risk for worse survival.
• Obese patients who received chemotherapy had significantly worse survival
outcomes.
• Overweight patients who received tamoxifen had significantly better
survival outcomes.
SAN ANTONIO — Obesity is associated with worse outcomes overall in early-stage
breast cancer, researchers reported at the 2011 CTRC-AACR San Antonio Breast Cancer
Symposium, held Dec. 6-10, 2011.
Obesity was linked to shorter time to recurrence (TTR), disease-free survival (DFS) and
overall survival (OS). The exception was treatment with endocrine therapy (mainly
tamoxifen), in which obesity was associated with a protective effect.
“The findings add to the body of evidence indicating that obesity, in general, increases a
patient’s chance for having a worse prognosis,” said lead researcher Sao Jiralerspong,
M.D., Ph.D., an assistant professor of medicine at Baylor College of Medicine.
“Obesity is a probable risk factor for worse breast cancer outcomes, and ours is the latest
study to suggest it has an effect on treatment outcome as well,” Jiralerspong said.
Using data from the Lester and Sue Smith Breast Center at Baylor, Jiralerspong and
colleagues examined the link between weight and treatment modality in 4,368 patients
treated between 1970 and 1995.
For the group as a whole, data revealed that overweight patients had similar outcomes to
normal-weight patients, but obese patients had an increased risk for worse TTR, DFS and
OS.
December 7, 2011
Today's abstracts reaffirm the benefits of using Zometa with endocrine therapy to prevent recurrence. There is now a test for recurrence risk in DCIS patients. The poor prognosis of overweight women is further studied. And, directly in line with our Before Forty Initiative, Hispanic women are diagnosed younger than non-hispanics and are more likely to develop a very aggressive, non-responsive form of Triple Negative Breast Cancer. They have a high mortality rate. Imagine if our Before Forty Initiative was able to help these women? We are working hard to do just that. Abstracts below. More to follow tomorrow.
Immediate Bisphosphonate Use With Endocrine Therapy Reduced
Recurrence, Increased Survival in Postmenopausal Early Breast Cancer
• Long-term data confirm overall survival benefit with zoledronic acid.
• Women five years postmenopause had greatest benefit.
• Even delayed use of zoledronic acid reduced recurrence vs. no use.
SAN ANTONIO — The addition of zoledronic acid to adjuvant endocrine therapy
increased bone mineral density and reduced the risk for disease recurrence among
postmenopausal women with early hormone receptor-positive breast cancer, according to
new data from the ZO-FAST trial.
Richard de Boer, M.D., of the Royal Melbourne Hospital in Victoria, Australia, presented
long-term data from the Zometa-Femara Adjuvant Synergy Trial (ZO-FAST) at the
2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.
De Boer and colleagues explored adding zoledronic acid, an intravenous bisphosphonate,
to adjuvant endocrine therapy to reduce bone mineral density loss seen with aromatase
inhibitors and to improve survival outcomes.
When he presented initial data from ZO-FAST at the 2010 CTRC-AACR San Antonio
Breast Cancer Symposium, de Boer indicated that early zoledronic acid resulted in a
significantly improved bone mineral density and an improved disease-free survival. At
this year’s symposium, he reported long-term data and data on the effect of menopausal
status at breast cancer diagnosis on disease-free survival.
Researchers randomly assigned 1,065 patients who were about to commence letrozole, an
aromatase inhibitor, to receive immediate zoledronic acid every six months or to a
delayed group where zoledronic acid was started at a later time only if the patient
experienced a fracture or a documented fall in bone mineral density.
Immediate Bisphosphonate Use With Endocrine Therapy Reduced Recurrence,
Increased Survival in Postmenopausal Early Breast Cancer
Page 2 of 2
After 60 months of follow-up, “the primary endpoint of the trial was successfully
achieved — up-front zoledronic acid significantly decreased bone mineral density loss in
both the lumbar spine and the hip,” de Boer said. “The secondary endpoint of an
improvement in disease-free survival was also met with a 34 percent decrease in disease
recurrence in the patients receiving the up-front zoledronic acid.”
Researchers conducted an exploratory subgroup analysis based on menopausal status at
the time of breast cancer diagnosis. Data indicated that in women who were truly
menopausal at diagnosis, immediate treatment with zoledronic acid reduced the risk for
disease recurrence by 29 percent and improved overall survival by 35 percent.
“In addition, patients in the delayed group, who did not start with zoledronic acid but
who switched to start at a later time, also appeared to benefit from the zoledronic acid
with an improvement in disease outcomes compared with those women who never started
the bisphosphonate,” de Boer said.
Additional studies are needed to fully define the patient populations most likely to benefit
from adjuvant zoledronic acid in this setting.
Until then, “patients with hormone receptor-positive breast cancer who are
postmenopausal and about to commence letrozole have the option of considering the
addition of zoledronic acid — primarily to maintain bone mineral density but also with
the aim of reducing the risk for disease recurrence,” de Boer said.
# # #
Presenter: Richard de Boer, M.D.
Abstract Number: S1-3
Title: Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-
Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year
Follow-Up of ZO-FAST.
Author Block: R de Boer1, N Bundred2, H Eidtmann3, P Neven4, G von Minckwitz5, N Martin6,
A Modi6 and R Coleman7. 1Royal Melbourne Hospital, Victoria, Australia; 2University Hospital
of South Manchester NHS Foundation Trust, Manchester, United Kingdom; 3University
Frauenklinik, Kiel, Germany; 4Breast Clinic, UZ Gasthuisberg, Leuven, Belgium; 5German
Breast Group, Frankfurt, Germany; 6Novartis Oncology, East Hanover, NJ and 7University of
Sheffield, Sheffield, United Kingdom.
Introduction: Recent clinical trials suggest potential anticancer activity for bisphosphonates
combined with adjuvant endocrine therapy in patients with hormone receptor-positive (HR+)
early breast cancer (EBC). Data from the interim analysis of AZURE suggest that the benefits of
adding zoledronic acid (ZOL) may be greatest in patients with low estrogen levels (Coleman RE,
et al. SABCS 2010). In ZO-FAST, we have previously demonstrated that adding ZOL to
adjuvant therapy significantly improved bone mineral density (BMD) and prolonged disease-free
survival (DFS) vs delayed ZOL (de Boer R, et al. SABCS 2010). We report here the effect of
time since menopause at breast cancer diagnosis (ie, baseline menopausal status) on DFS
benefits with ZOL.
Methods: Postmenopausal women with HR+ EBC receiving letrozole (LET; 2.5 mg qd × 5 yr)
with a BMD T-score ≥–2 (N=1065) were randomized to ZOL (4 mg q6mo): immediate (IMZOL)
or delayed (DZOL; initiated for postbaseline T-score <–2 or nontraumatic/asymptomatic
fracture). Patients were followed for disease recurrence and overall survival (OS) for 5 years.
Patients were eligible for the study if they had established menopause at the time of diagnosis, or
if they became menopausal because of chemotherapy or ovarian suppression (ie, recently
postmenopausal). The effect of baseline menopausal status on DFS was examined in Cox
regression analyses.
Results: At 60 months' follow-up in the overall population (N=1065), IMZOL significantly
reduced the risk of a DFS event by 34% vs DZOL (hazard ratio [HR]=0.66; 95% confidence
interval [CI], 0.44-0.97; P=.034). In exploratory analyses of women who were postmenopausal
for >5 years or >60 years old at study entry (n=670), IMZOL improved DFS (HR=0.63; 95% CI,
0.39-1.01; P=.052) and significantly prolonged OS (HR=0.50; 95% CI, 0.27-0.92; P=.022) vs
DZOL. Additional subgroup analyses including patterns of breast cancer recurrence will be
presented. During 5 years of treatment, osteonecrosis of the jaw (ONJ) was reported in 4/669
patients (0.6%) who received ZOL, and there was no increase in renal adverse events (AEs) in
the ZOL-treated patients. Overall, AEs were consistent with the known safety profiles of both
study drugs.
Conclusions: Long-term follow-up in ZO-FAST confirms the overall survival benefits of adding
ZOL (4 mg q6mo) to adjuvant LET therapy for EBC. However, subset analyses suggest that
women with established postmenopausal status may benefit from ZOL therapy more than others.
These results are consistent with observations in the AZURE trial, and support potentially greater
ZOL benefits in a low-estrogen environment. Additional studies are needed to fully define the
patient populations most likely to benefit from adjuvant ZOL in this setting.
###
New Test Predicts Risk for Recurrence for
Patients With DCIS
• Multigene assay predicts risk for local recurrence for patients with DCIS.
• This advance combines knowledge of the genome and new molecular
technologies.
• Test allows physicians to individualize treatment so that lower-risk patients
avoid radiation.
SAN ANTONIO — In a significant advance for patients with ductal carcinoma in situ,
researchers have developed and prospectively validated a multigene test to identify the
risk for recurrence of breast cancer.
The method combines measuring tumor gene expression with a gene expression
algorithm to decipher the genetic underpinnings of a patient’s cancer and determine
whether the individual patient should be treated with surgery (usually lumpectomy) or a
combination of surgery and radiation.
This is the first time a multigene test has been used to differentiate lower-risk and more
aggressive forms of ductal carcinoma in situ (DCIS) and will allow physicians to spare
many patients the need to undergo radiation, according to researchers.
Lawrence J. Solin, M.D., FACR, FASTRO, chair of the department of radiation oncology
at Einstein Medical Center in Philadelphia, presented the results at the 2011 CTRC-
AACR San Antonio Breast Cancer Symposium (SABCS), held Dec. 6-10, 2011.
“Using a molecular-based assay, we have successfully identified patients at higher risk
for recurrence and patients at lower risk,” said Solin. “This is an important advance for
women with newly diagnosed DCIS. By predicting individual risk, physicians can
provide a more tailored treatment program for each patient.”
The validation study of the DCIS Score was a collaboration among the Eastern
Cooperative Oncology Group (ECOG), North Central Cancer Treatment Group and
Genomic Health. The validation utilized patient tumor samples from E5194, an ECOG-
led, multi-institutional study of patients with low-, intermediate- or high-grade DCIS who
had been treated surgically but had not received radiation. E5194 was the first
prospective study of local excision alone for DCIS, and its five-year results were reported
at SABCS in 2006 (L. Hughes).
Researchers tested and scored tumors from 327 patients to determine their risk for
recurrence. The DCIS validation study team used the Oncotype DX breast cancer assay,
which has been available for invasive breast cancer since 2004, and a DCIS Score
algorithm to study these tumor samples.
The test uses reverse transcriptase-polymerase chain reaction technology, which
quantitates the level of RNA in the individual tumor sample to reveal its underlying
biology. The level of RNA is then used by a prespecified algorithm to calculate a DCIS
Score, which predicts the likelihood of local recurrence, defined as either the
development of a new invasive breast cancer or the recurrence of DCIS.
Solin also reported 10-year results of E5194, in which 46 patients had an ipsilateral breast
event (IBE; defined as ipsilateral local recurrence of DCIS or invasive cancer) at a
median follow-up of 8.8 years. Continuous DCIS Score was significantly associated with
IBE when adjusted for tamoxifen use and provided value beyond the traditional measures
of tumor size, tumor grade and margin status.
Numerous studies, including the current study, have shown that routine, microscopic
pathology grading is not a reliable indicator of the risk for recurrence.
“The DCIS Score will help physicians understand the underlying biology of DCIS for an
individual patient and accurately gauge the risk for that person,” said Solin. “As a result,
the patient and physician can decide on the appropriate course of treatment based on a
more complete understanding of the risk involved.”
# # #
Presenter: Lawrence J. Solin, MD, FACR, FASTRO
Abstract Number: S4-6
Title: A Quantitative Multigene RT-PCR Assay for Predicting Recurrence Risk after Surgical
Excision Alone without Irradiation for Ductal Carcinoma In Situ (DCIS): A Prospective
Validation Study of the DCIS Score from ECOG E5194.
Author Block: Lawrence J Solin1, Robert Gray2, Frederick L Baehner3, Steven Butler3, Sunil
Badve4, Carl Yoshizawa3, Steven Shak3, Lorie Hughes5, George Sledge6, Nancy Davidson7, Edith
A Perez8, James Ingle9, Joseph A Sparano10 and William Wood11. 1Radiation Oncology, Albert
Einstein Medical Center, Philadelphia, PA; 2Eastern Cooperative Oncology Group, Boston, MA;
Genomic Health, Inc., Redwood City, CA; 4Pathology, Indiana University, Indianapolis, IN;
North Georgia Radiation Therapy, The Hope Center, Cartersville, GA; 6Medical Oncology,
Indiana University, Indianapolis, IN; 7Medical Oncology, University of Pittsburgh, Pittsburgh,
PA; 8Medical Oncology, Mayo Clinic Jacksonville, Jacksonville, FL; 9Medical Oncology, Mayo
Clinic Rochester, Rochester, MN; 10Medical Oncology, Albert Einstein College of Medicine,
Bronx, NY and 11Surgery, Emory University, Atlanta, GA.
Background: We have previously reported the results of surgical excision without irradiation for
selected patients with DCIS in ECOG E5194, where the 5-year rates of local recurrence varied
with age, grade, and lesion size (Hughes et al. J Clin Oncol 27:5319, 2009). New methods are
needed to provide more accurate and reproducible assessment of recurrence risk.
Methods: ECOG E5194 included 670 eligible patients with DCIS treated with surgical excision
(≥ 3 mm negative margins) without irradiation, 228 of whom received tamoxifen. Patients had
low or intermediate grade DCIS ≤ 2.5 cm, or high grade DCIS ≤ 1 cm. The Oncotype DXR assay
was performed by quantitative RT-PCR using formalin fixed paraffin embedded tumor
specimens from 327 patients (49% of the parent study). Recurrence ScoreR (RS) was calculated
using the published algorithm. A new, prespecified DCIS Score™ was designed to predict
recurrence using an optimized gene expression algorithm. The primary objective was to
determine whether there was a significant association between the risk of an ipsilateral breast
event (IBE) and the continuous DCIS Score in Cox models. 46 patients had an IBE (defined as
ipsilateral local recurrence of DCIS [n=20] or invasive cancer [n=26]). Median follow-up was
8.8 years.
Results: The 10-year IBE rates were 15.4% for low/intermediate grade DCIS and 15.1% for
high-grade DCIS (as determined by central pathology review), and for invasive IBE, 5.6% and
9.8%, respectively. Comparison between local and expert grading showed substantial
disagreement. Continuous DCIS Score was significantly associated with IBE (HR 2.34 per 50
units; 95% CI 1.15, 4.59; p=0.02) when adjusted for tamoxifen use (prespecified primary
analysis) and with invasive IBE (HR 3.73; CI 1.34, 9.82; p=0.01). DCIS Score was significantly
associated with outcome when evaluated by the prespecified risk groups (see Table). Similar
results were observed with and without adjustment for tamoxifen use or for negative margin
width. Features associated with IBE in multivariate models included menopausal status (HR
0.49; 95% CI 0.27, 0.90; p=0.02), tumor size (HR 1.52 per 5 mm; 95% CI 1.11, 2.01; p=0.01),
and continuous DCIS Score (HR 2.41; 95% CI 1.15, 4.89; p=0.02). The standard RS, which is
calculated using thresholding of many genes unlike the DCIS Score, was not associated with IBE
or invasive IBE (p > 0.6).
Conclusions: We have prospectively validated a multigene assay that quantifies recurrence risk
and complements traditional clinical and pathologic factors in selected patients with DCIS
treated with surgical excision without irradiation. The DCIS Score provides a new clinical tool
for individualized selection of treatment for patients with DCIS.
Breast Cancer Mortality Higher in Hispanic Women
Hispanic women had a 20 percent increased risk for death from breast
cancer. Tumor-related factors may primarily account for this difference.
Hispanic women may be more likely to have a tumor phenotype resistant to
chemotherapy.
SAN ANTONIO — Hispanic women are more likely to die from breast cancer than non-
Hispanic white women, according to research presented at the 2011 CTRC-AACR San
Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.
“This difference may be associated with a tumor phenotype that is less responsive to
chemotherapy,” said Kathy B. Baumgartner, Ph.D., professor of epidemiology and
associate dean for faculty affairs in the School of Public Health and Information Sciences
at the University of Louisville in Kentucky. “Increased awareness of this ethnic disparity
is needed to improve survival in Hispanic women with breast cancer.”
Breast cancer is the most common cancer and is the second cause of cancer death in
women in the United States. Incidence and survival rates vary by ethnicity, and previous
research has demonstrated a trend toward poorer survival in Hispanic women.
From 1992 to 1996, Baumgartner and colleagues conducted the New Mexico Women’s
Health Study (NMWHS), a statewide, population-based, case-control breast cancer study
that examined the difference between Hispanic and non-Hispanic white women for breast
cancer risk. In all, 692 women with a first primary breast cancer participated.
In a recent study, researchers followed the 577 women with invasive breast cancer
through 2008 to assess differences in long-term survival between Hispanic and non-
Hispanic white women in the NMWHS.
Hispanic women were about 20 percent more likely to die from breast cancer than non-
Hispanic white women, which is consistent with other reports, Baumgartner said. After
adjusting for age, stage, lymph node involvement and estrogen receptor (ER) status, the
researchers saw the risk drop considerably to almost equal that of non-Hispanic white
women — suggesting that “the ethnic difference in breast cancer mortality may be mostly
biologically based,” Baumgartner said.
In addition, Hispanic women who received chemotherapy were about 1.5 times more
likely to die from breast cancer compared with non-Hispanic white women who received
chemotherapy, after adjusting for age and the characteristics noted above.
“It is not clear how much of this ethnic difference in survival is due to socioeconomic
factors influencing access to screening and treatment or to biological ones,” Baumgartner
said. “Some studies suggest that Hispanic women are more likely to develop ER-negative
tumors that are resistant to chemotherapy.”
She added, “Altered response to chemotherapy may partly explain the Hispanic vs. non-
Hispanic white disparity in breast cancer survival.”
There was no difference between Hispanic and non-Hispanic white women for all-cause
or non-breast cancer mortality.
Baumgartner and her colleagues will continue to monitor this cohort for the long term.
This research was supported by a grant from the National Cancer Institute and the James
Graham Brown Cancer Center.
# # #
Presenter: Kathy B. Baumgartner, Ph.D.
Abstract Number: P1-08-28
Title: Differences in long-term survival for Hispanic and non-Hispanic white women with breast
cancer.
Author Block: Kathy B Baumgartner1, Christina M Pinkston2, Stephanie R Denkhoff3 and
Richard N Baumgartner4. 1Epidemiology & Population Health, School of Public Health &
Information Sciences, University of Louisville, Louisville, KY, United States; 2Epidemiology &
Population Health, School of Public Health & Information Sciences, University of Louisville,
Louisville, KY, United States; 3Epidemiology & Population Health, School of Public Health &
Information Sciences, University of Louisville, Louisville, KY, United States and 4Epidemiology
& Population Health, School of Public Health & Information Sciences, University of Louisville,
Louisville, KY, United States.
Body: Trends towards poorer survival in Hispanic (H) women have been previously reported, but these studies are limited by small sample sizes or lack of sufficient covariate data. Overall, H women are more likely to be diagnosed with breast cancer at a younger age, with hormone receptor negative tumors, with more advanced stage at diagnosis, and with worse prognosis.
Data are limited on survival experience for H women, leading to unanswered questions and concerns, as this ethnic group is a rapidly growing fraction of the U.S. population. Although survival can be evaluated based on national data, important covariates are lacking. The analyses for this study focus on survival differences between H and non-Hispanic white (NHW) women and factors associated with this difference.
Previous reports suggest that breast cancer survival is significantly worse in H compared to NHW women, even with adjustment for age, stage, histology, and treatment. The New Mexico Women's Health Study (NMWHS) was a statewide population-based, case-control breast cancer study that included 1,566 H and NHW women conducted from 1992-1996. It was designed to investigate etiologic risk factors associated with the difference in breast cancer incidence between H and NHW women. Women diagnosed with a new primary in situ or invasive breast cancer were ascertained through the New Mexico Tumor Registry (NMTR) and eligibility was based on the following criteria: age 20-74 years, diagnosis year 1992-1994, and New Mexico residence at diagnosis. All identified H cases and approximately 33% of identified NHW cases comparable to the age and geographic distribution of H cases were eligible for the study.
Of the 984 eligible cases identified, 73% completed an interview: 339 H (69%); 388 NHW (78%). The National Death Index (NDI) was used to determine vital status through December 31, 2008, the most recent date for which NDI data are available. Data for clinical and tumor characteristics were obtained through linkage with the NMTR. The respective crude hazard ratios (HR) for all-cause, breast cancer-specific, and non breast cancer mortality over the 14-year follow-up period for H women compared with NHW women were 1.09 (95%CI 0.84-1.42), 1.29 (0.91-1.84), and 0.88 (0.59-1.31), respectively.
These results suggest that breast cancer-specific mortality, is increased in H relative to NHW women, while there is no ethnic difference in all-cause or non-breast cancer mortality. Restriction of the analysis for breast cancer mortality to cases with invasive cancer (n=692) did not meaningfully alter the crude HR for H women (HR=1.24, 95%CI 0.84-1.74). Evaluation of breast cancer mortality by ethnicity and chemotherapy treatment, adjusting for stage of disease, lymph node and estrogen receptor status suggested that H women receiving chemotherapy have worse survival (p=0.052 for statistical interaction), which may be due to factors such as altered
response to chemotherapy or possibly poor compliance.
###
Obesity Linked to Worse Outcomes in Early Breast Cancer Treatment
• In the overall group, obese patients had an increased risk for worse survival.
• Obese patients who received chemotherapy had significantly worse survival
outcomes.
• Overweight patients who received tamoxifen had significantly better
survival outcomes.
SAN ANTONIO — Obesity is associated with worse outcomes overall in early-stage
breast cancer, researchers reported at the 2011 CTRC-AACR San Antonio Breast Cancer
Symposium, held Dec. 6-10, 2011.
Obesity was linked to shorter time to recurrence (TTR), disease-free survival (DFS) and
overall survival (OS). The exception was treatment with endocrine therapy (mainly
tamoxifen), in which obesity was associated with a protective effect.
“The findings add to the body of evidence indicating that obesity, in general, increases a
patient’s chance for having a worse prognosis,” said lead researcher Sao Jiralerspong,
M.D., Ph.D., an assistant professor of medicine at Baylor College of Medicine.
“Obesity is a probable risk factor for worse breast cancer outcomes, and ours is the latest
study to suggest it has an effect on treatment outcome as well,” Jiralerspong said.
Using data from the Lester and Sue Smith Breast Center at Baylor, Jiralerspong and
colleagues examined the link between weight and treatment modality in 4,368 patients
treated between 1970 and 1995.
For the group as a whole, data revealed that overweight patients had similar outcomes to
normal-weight patients, but obese patients had an increased risk for worse TTR, DFS and
OS.
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