It wasn’t red M&Ms or sitting too close to the TV or your underwire bra that caused your breast cancer. Instead, almost all breast cancer results from random mutations of healthy cells. A single cell must first have a change or mutation in its DNA. Then another mutation occurs and the cells divide and create more cells that mutate and start duplicating. It is amidst this chaos that single cancer cells form tumors and create their own identities, taking on so many configurations and qualities that no two breast cancers are ever exactly alike. Some grow faster and others slower. Some inhabit milk ducts and others the lymph nodes. Some are spurred to grow with exposure to estrogen, others through overabundance of a tumor-driving protein called Her2 neu.
Even though no two breast cancers are identical, doctors must know as much as possible about each woman’s breast cancer in order to optimize her treatment and the chance she can be cured. That’s where the biopsy (the surgical sampling of a piece of the tumor) and the resulting pathology report comes in. To characterize a cancer prior to treatment, doctors send the tumor down to a pathology lab, where they analyze as many of its physical and biological characteristics as possible.
The one thing I hear the most from newly diagnosed women is, “My doctor just told me about my path report. What does it mean?” I found this one of the most frightening parts of my personal cancer journey, as well. To me, knowing my pathology was the whole ball game – whether I would live or die, if I had to do chemo, everything. The day I was to hear my path report I was so overwhelmed by fear I could barely walk. It felt like sentencing day: was I going to get life in prison or the death penalty? I remember pressing the elevator button to my doctor’s floor and when the doors opened I WAS paralyzed with fear. I didn’t know what a path report meant except that it had to be bad. And now it was time to learn my fate.
I wasn’t exactly right. Yes, your pathology is an extremely important factor in determining your treatment protocol. But will it tell you if you will live or die? No. Instead, the pathology report literally puts your cancer under the microscope, providing as many clues as possible to its size, its location in your body, the likelihood that it will spread, and the ways you can treat it best.
Different pathology reports may be laid out or presented in different ways, but all will reference the following:
When a surgeon operates on you he will usually be able to identify your cancer as either Invasive (broken through its original location, such as the milk duct or lobule and infiltrated surrounding breast tissue) or InSitu (remaining confined within the milk duct or lobule, or wherever it began). After this crucial step, the tumor is removed from its resting place and sent directly to the pathology lab. At this time the margins will also be checked. “Margins” are the healthy tissue that surrounds a tumor. If a surgeon can remove your tumor and the pathologist finds no cancer in the tissue that is attached to it, that is known as “getting a clean margin.” If there is cancer found in the margin, the surgeon must re-excise the tumor, meaning re-operate, to remove more tissue to ensure that all the cancer cells have been removed. If a clean margin cannot be obtained, usually a mastectomy is recommended.
The first thing that the pathologist does is measure you tumor’s size, with the smaller tumors generally indicating the earlier stages of the disease. If the tumor is less than a centimeter in size, you have most likely caught the cancer early, before it has had a chance to do much harm; the larger it gets, the more likely it is to have spread.
Along with the tumor, the surgeon will have removed one or more lymph nodes, which transport the protein-rich fluid known as lymph and its associated immune cells throughout the body. The axillary lymph nodes, where your breast filters to, are located under your arm in a little bundle of fat. That bundle can hold from 5 up to 40 nodes. If you were to get the traditional surgery of complete lymph node dissection the surgeon would remove that entire bundle. It would then be sent to the path lab for the cytologist to sort out.
A newer and preferred procedure is the Sentinel Node Biopsy. This was created to minimize the amount of lymph nodes removed. Your surgeon will inject a tracer dye into your tumor field to see which node the dye goes to first. That first one is the sentinel node. The nodes surrounding it are then watched to see if they collect the dye as well. Usually two or three are sent dye from the sentinel node. These are removed and tested. If they are clear, the chances are the rest of the nodes in the axillary sac are also clear and no further surgery is required. If there is cancer found in them then the sac will be removed.
Next, the molecular receptors on the surface of your cancer cells are measured. If your tumor has plentiful estrogen and progesterone receptors, you will be designated estrogen and progesterone positive (ER/PR+). If it does not, you are estrogen and progesterone negative (ER/PR-). If you have a tumor that is fueled by estrogen, then there are medications that will be added to your treatment protocol that will help fight the cancer by blocking the estrogen. It is considered a good sign because there are several anti- estrogen drugs available and they have shown great success. While there are no drugs currently available for women who have negative estrogen and progesterone receptors, several clinical studies have shown that those types of tumors have a better response rate to chemotherapy.
Another thing you will be tested for by the pathologist is the presence of the Her-2/neu oncogene, which makes a protein that promotes cancer cell growth. If the gene and its protein are found in great abundance in your tumor, that means your cancer is fast-growing and the protein is encouraging more cancer cells to grow. You will be classified as HER2 positive (HER2+). Almost twenty-five percent of women have the HER2 protein present in their tumor. Until very recently, having a HER2 positive diagnosis was not a good thing. Doctors had no way of counteracting the protein. As a result, the prognosis was poor –until the drug called Herceptin (Trastuzumab) hit the scene.
Herceptin works differently than chemotherapy. Imagine a regular cancer cell as a plain M&M and a Her2 positive cancer cell as a peanut M&M. FIRST the chemo comes in and kills the chocolate candy of the regular cell and the cancer is eradicated. But the Her2 positive cancer still has the peanut underneath the chocolate candy. So the Herceptin is used after chemo to go in and take out the peanut, eradicating everything. Like the peanut, Once the HER2 protein that is promoting cancer growth is removed, the prognosis becomes very good for HER2 Positive women.
Breast cancer by type
As you read your pathology report, you are likely to see your breast cancer labeled in the following ways:
Ductal Carcinoma in Situ (DCIS) is cancer at its beginning. The cells have mutated and divided and begun to proliferate but they have remained inside the milk duct.
Infiltrating or Invasive Ductal Carcinoma (IDC) is a cancer that has broken through the milk duct membrane and grown to become a lump or tumor. When a pathologist examines it later, he will be able to measure how fast it grew and how aggressive it was by how many of the cells are dead, (necrosis), how many new cells are created (mitosis) and what role the DNA played in this cycle.
Infiltrating or Invasive Lobular Carcinoma (ILC) make up 25% of breast cancers. This means that it occurs in the actual lobules that produce milk. Because it is hard to see on mammography, the tumors are usually discovered later and therefore larger, until it breaks through the wall of the milk lobule. Invasive lobular is hard to detect because rather than forming a lump it grows in what has been described as sheets or leaves. If you imagine a branch of a tree and the leaves filling out and growing, that is essentially how lobular cancer appears when it is spreading.
Lobular Carcinoma In Situ (LCIS) is now being classified in a new way. Once it was thought to be just like its cousin DCIS- a pre-cancer or Stage 0 cancer. There has been a shift in perception. Now researchers have discovered that having LCIS may increase a woman’s chances of getting invasive cancer, but it is not a guarantee. The cells found could sit dormant for a woman’s lifetime, making it also referred to as a “neoplasm” or pre- malignancy.
Inflammatory Breast Cancer presents itself with swelling, a feeling of heat inside the skin, a red tinge to the breast area and the breast sometimes swells up too. In some cases dark red or purple stripes may appear across the chest. The skin may pucker inwards like the skin of an orange and that can be explained away as a side effect of the swelling. At first glance a doctor would view a swollen, hot breast with a rash and declare mastitis, which is a breast infection. Antibiotics are given and nothing helps. Sometimes it may take several visits to the doctor or even a change in doctors before the possibility of IBC is investigated.
Paget’s disease is sometimes cancerous, but not always. When it is cancer, it is a type of in situ cancer that can begin in the ducts of the nipple. It grows close to the skin or the nipple and then can appear like IBC does with the swelling, heat and the orange peel skin. There may also be an itchy rash and a bloody discharge from the nipple, which can become inverted.
Medullary carcinoma is a cancer with the best prognosis of all. It is clearly identifiable and not as aggressive as the other breast cancers. Only a very small percent of women are diagnosed with Medullary cancer. However, women who carry the breast cancer gene mutation, BRCA 1, have a greater chance of developing Medullary cancer.
Phyllodes can be found in the breast tissue that surrounds the ducts and lobules. Most often such tumors are not cancerous. However, if they are, they do not respond to the traditional therapy that is effective on ductal or lobular cancers. The treatment consists of surgery, either by lumpectomy or mastectomy.
Cancer by Stage
Stage 0: InSitu cancer
Stage1: Tumor is under 2 centimeters and there is no lymph node involvement
Stage2: Tumor is larger than 2 cm but smaller than 5 cm and may or may not have spread to the lymph nodes under the arm of the affected side. No other tissue is affected and the lymph nodes are not attached to one another.
Stage 3A: Tumor is larger than 5 cm and lymph nodes of affected side are positive and are attached to one another.
Stage 3B: Any tumor that has spread to the chest wall, skin, and lymph nodes of the armpit, breast, and chest.
Stage 4: The tumor can be of any size but the cancer has spread to another part of the body, bones, lungs and other lymph nodes.
Next they take this stage and add on the prognosticator factors that can be found in the genes, through hormone receptors, and whether the tumor was aggressive or not.
Your Pathologist will also GRADE your tumor.
The faster a cancer spreads, the more dangerous it is. If your tumor is slow growing, the pathologist will be able to tell the difference between the healthy cells and the cancer cells. That is called “well differentiated” on your path report. As it becomes harder to differentiate between healthy cells and cancer cells, the path report may refer to the situation as anywhere from “moderately differentiated” to “poorly differentiated.” In a poorly differentiated tumor the cells have grown so fast that the pathologist cannot tell the healthy ones apart from the dead ones. This designation appears on your pathology report as the S-Phase. It simply means the speed with which your cancer grew.
The path report also designates how aggressive your cancer is by giving it a grade. (Do not confuse the “grade” of your cancer with your cancer’s “stage,” which we cover below.) Knowing your cancer grade is almost like knowing the horsepower of your car. How fast can this thing go? To come up with your cancer’s horsepower, various factors are calibrated in what is known as the Bloom Richardson Scale –referred to as a B/R score on your pathology report. The score can range from 3 (very slow moving) to 9 (very fast-paced.) The grade you get takes the following into account:
This “aggressiveness” grading system tells the pathologist just how ambitious your tumor really was. It looks at the following three things:
If the cell has formed tubular features
Tubules are part of the architecture that along with the other components, make up a cancer cell.
If there are a lot of tubular features, then the tumor is slow growing and less aggressive.
The “nuclear grade” meaning the activity of the DNA
This measures the nucleus of the DNA of the cancer cell to see how fast the cells divided to create more cancer cells.
If a tumor has a high nuclear activity it means that it is a faster growing cancer.
How many cells divide at once, also known as the mitotic rate, which means the rate at which new cells were created.
The lowest you can score on this scale is 3 (grade 1). That is the best score because that means you have a very slow growing, non- aggressive cancer. The highest is 9 (grade 3) meaning your cancer cells are rapidly dividing and very aggressive.
BLOOM RICHARDSON SCALE
Means your B/R score was between 3-5
Means your B/R score was between 6-7
Means your B/R score was between 8-9
Remember! Don't confuse your GRADE with your STAGE!
You can score a Grade 3 but still have a Stage 1 cancer. For example, if you have a highly aggressive cancer that scores high on the Bloom/Richardson scale but the tumor itself is still small and has no lymph node involvement, you will have a stage one cancer.
Grade 1- B/R score was between 3-5. This is a very slow-growing
Grade 2 - B/R score was between 6-7. This is an intermediate growing
Grade 3 - B/R score was between 8-9. This is a fast-growing
How this all applies to YOU
It is important to note that two women with nearly identical pathology reports may not have the same prognosis or outcome. Many things factor into your own body’s response to your particular cancer, the state of your immune system and your genetic make up. Never judge your prognosis on the basis of someone else’s experience. You simply cannot compare. We are too uniquely individual to be able to ever do that.
As they say, knowledge is power. I was powerless when I went to see my doctor to hear my pathology report because I did not understand what any of it meant. Now, you have a clear idea of what will be discussed. Of all the things to learn during this confusing time, the most important is to remember to breathe. As the days pass and things get sorted out, you will feel better. The road ahead will be clearer and –guided by your doctor and the details in your pathology report―you’ll be ready to take on cancer head on and conquer it with the best weapons we have.
A Tale of Two Path Reports
The following are two actual pathology reports. As you can see, they all do not look the same. But the basic information is there and easy to recognize now that you know what to look for.
The first pathology report is for an invasive ductal carcinoma that was removed by lumpectomy. It has negative estrogen and progesterone receptors and is also Her2 negative. There was a complete axillary dissection and none of the lymph nodes were involved.
The second pathology report is for a woman who had a mastectomy. It shows that she had invasive lobular carcinoma and it is responsive to estrogen and progesterone. She is Her2 negative. The report shows that a sentinel node biopsy was attempted, but the sentinel node came back positive for cancer, so her entire axillary sac was removed. After testing, it revealed that she had four positive lymph nodes and the cancer did spread outside the lymph nodes but remained in the axillary bundle.
Surgical Pathology Report #1
Specimen: Lt Breast Mass
Clinical diagnosis and History: Left Breast Mass
A. Type and Size of Carcinoma:
1. Infiltrating Ductal, Solitary, Size 1.3x1.0 cm
2. Intraductal Present, Solitary
B. Histologic Grade, SBR Score: 7/9
1. Nuclear grade High
1. For invasive ca: Positive, Superior, inferior, deep
2. For non-invasive ca: Positive
D. Vascular Invasion: Absent
E. Axillary Lymph nodes: 27/negative
1. Estrogen Receptor Negative
2. Neoplastic Cells 0%
3. Progesterone Receptor Negative
4. Neoplastic Cells 0%
1.Cytoplasmic membrane staining Negative
2.Score: 0 (X), 1+ ( ), 2+ ( ) , 3+ ( )
H. DNA Analysis
1. Anaploid 9 (High)
2. S-phase 8% (> 8% High)
3. Ki-67 Staining 50% (> 10% High)
Remarks: Slides labeled 01-4593, representing the left breast excision, show an invasive ductal carcinoma, poorly differentiated, associated with Ductal Carcinoma In Situ (DCIS) with high nuclear grade, apocrine features, and necrosis. The DCIS is noted at the periphery of and away from the invasive component. The INVASIVE carcinoma measures 0.9 cm microscopically on slide labeled 01-A4593. Both invasive and DCIS are very close to the inked margins. I see no convincing evidence of lymphovascular invasion.
What it said:
This woman had a small tumor that began as DCIS and became invasive. It is estrogen/progesterone receptor negative, it is very aggressive because the tumor had a high S-phase, Ki-67 phase and a B/R score of 7/9. The good news is she has no positive nodes, is HER2 negative, and has no vascular invasion.
What will happen to her? If she had an ER/PR positive tumor, and a less aggressive cancer, she probably could get only a lumpectomy and radiation. The gray area of chemo or no chemo is an under one centimeter tumor, with an ER/PR positive tumor and a very un-aggressive cancer.
However, because she had a small tumor, a lumpectomy with radiation is still the only surgery she will require and a course of prophylactic chemotherapy would be the safest route.
Surgical Pathology Report #2
Invasive Lobular Carcinoma
Size of Carcinoma: 2.5 cm
Tubule formations: 3
Nuclear pleomorphism: 3
Total Score: 7/9
Margins: Uninvolved by carcinoma (distance from closest, deep margin is 1.1 cm)
Lymph node status
Total number of lymph nodes: 29
Number of nodes with tumor: 4
Extranodal extension: present
Skin: Not involved in Tumor
Microcalcifications: present in non-neoplastic tissue
Pathological Staging: pT2. pN2A, pMX
Hormone Receptor Status:
Estrogen Receptor: Positive
Progesterone Receptor: Positive
0 ( ) 1 (x) 2 ( ) 3 ( )
1. Axilla (right, sentinel lymph node), excision -one (1) lymph node positive for metastatic carcinoma with perinodal extension
2. Breast and lower axillary contents (right), mastectomy
- infiltrating lobular carcinoma
3. Axilla (right, sentinel lymph node), excision -three (3) lymph nodes
What it said:
This woman had a mastectomy and started with a sentinel node biopsy. During the biopsy it was discovered that she had cancer in the sentinel node. The entire axillary sac was removed and later tested. Four lymph nodes out of the 29 removed tested positive for cancer. There also was extra-nodal extension which means that the cancer went outside the nodes, but remained confined to the axillary sac.
Her tumor was infiltrating lobular cancer, and estrogen and progesterone positive. She tested negative for the her-2/nue oncogene. When a pathology report labels a Her2 test result with a "0" or a "1" that means the cancer is not Her2 positive.
The good news is that this woman had a complete mastectomy and all the breast tissue has been removed. She is also responsive to hormones, so after a course of chemotherapy and radiation, she will be able to benefit from the hormone blocking drugs available to women who have cancer that is fueled by estrogen.