November 2004: Your Operative and Pathology Reports

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Lumpectomy, sentinal node dissection for IDC?

Question from Retha Ann: I've recently been diagnosed with infiltrating ductal carcinoma. My question is, how successful is lumpectomy with sentinel lymph node dissection in terms of ensuring a clean bill of health?

Answer —Beth DuPree, M.D., F.A.C.S.: Lumpectomy and sentinel lymph node biopsy is a very accepted and effective way to begin the treatment of early stage breast cancer. Long-term prognosis depends on the pathology report from that procedure.

There are other features that will play a role in determining the prognosis, such as the estrogen and progesterone receptors, HER2 status, lymphatic and vascular invasion, size of the tumor, and whether or not the sentinel lymph node—or other nodes—are involved with cancer cells. In addition, we'll be touching on other factors as we move through tonight's program.

Is one kind of biopsy better?

Question from alliecat: I'm scheduled to have a biopsy done next week. I don't know what kind of biopsy they will be doing. Is one biopsy method (needle, core needle, or Mammotome® biopsy) better than the other?

Answers —Beth DuPree, M.D., F.A.C.S.: First of all, you need to ask the physician what specific type of biopsy you're scheduled for. He or she will decide on what type of biopsy to perform depending on whether the abnormality they want to examine was seen on the mammogram, on the ultrasound, or found on the clinical exam. My personal preference is a Mammotome® biopsy, which is a procedure that uses a core needle device with one single insertion into the breast that takes multiple cores of tissue. Then, it's able to leave a tiny marker in the breast to highlight that area for future reference.

Ann Ainsworth, M.D.: A needle biopsy gives us a small amount of tissue to work with, a core needle biopsy gives us a little more, and a Mammotome® biopsy provides even more tissue. The more tissue you have, the easier it is to make the diagnosis because you have a lot of tissue to examine.

Marisa Weiss, M.D., president and founder: With the extra tissue, you can more easily get results on hormone receptors and HER2 status. These two pieces of information can help guide treatment, particularly if chemotherapy is recommended before surgery, hormonal therapy, and/or immune therapy.

Re-excision for close margins?

Question from Chrissy: My pathology report says that the margins were close. They are recommending doing a re-excision. Is this my best option?

Answers —Ann Ainsworth, M.D.: The surgical margins are examined by the pathologist. We ink the surgical surface so we can see the relationship between the tumor and the cut surface or surgical margin of the excision. The ink shows up on the slides we examine. Tumor cells can be at the surgical margins, close to the surgical margins, or the surgical margins can be negative (free of cancer). A close surgical margin means the tumor is 1-2 mm from the inked surface of the surgical excision.

Marisa Weiss, M.D., president and founder: The definition of a negative margin can vary from one hospital to another. At some institutions, if there is one normal cell between the cancer and the edge of the breast specimen (the margin), then the margin is called "negative."

Beth DuPree, M.D., F.A.C.S.: Re-excision is acceptable as long as the cosmetic results from the re-excision and subsequent radiation therapy are acceptable to the patient as an alternative to mastectomy.

HER2-positive cancer and chemotherapy?

Question from R. Lee: I have been told that my cancer was HER2 positive. What does that mean, and does it hinder my ability to respond to chemo?

Answers —Ann Ainsworth, M.D.: A positive HER2 test performed on a breast cancer means that the tumor has genes that are not normal. Cancers with too many copies of the HER2 gene or too much HER2 protein tend to be more aggressive and can be treated with an antibody to that extra gene's protein.

Marisa Weiss, M.D., president and founder: Cancers that have too much HER2 can have a very good response to chemotherapy. They tend to respond best to a chemotherapy that includes Adriamycin. They tend not to respond as well to CMF chemotherapy. Early results also show a good response to taxane chemotherapy (chemotherapy with Taxotere or Taxol). Cancers that are HER2 positive may have a better response to aromatase inhibitors than to tamoxifen.

It's important to know that this gene abnormality occurs during the course of your lifetime. In that way, the HER2 gene is different from the breast cancer genes, BRCA1 and 2, which are the kind of gene abnormalities that are passed from one generation to another and are called inherited gene abnormalities.

Test result differences in HER2 status?

Question from Mary: I was diagnosed with breast cancer a year ago. Initially on the needle biopsy path report, the HER2 result was "strongly positive." Then when the path report from the entire breast (post-mastectomy) came back, it said the tissue was HER2 negative. How could there be such a huge discrepancy in the two?

Answer —Marisa Weiss, M.D., president and founder: One cancer is usually made up of many different kinds of breast cells. We call this "tumor heterogeneity." It is possible that the sample removed initially did, in fact, have cancer that was HER2 positive and that the sample taken after treatment represented a different population within the cancer that was HER2 negative. The kind of difference in results that happen between samples is called the "sampling error."

It is also possible that you had HER2 positive cancer cells up front and that the treatment got rid of the HER2 positive cells, so that when the sample was taken after treatment, only the HER2 negative cells were left over. This is possible, but not necessarily likely.

Sometimes the results at one hospital or laboratory can differ from the results at another. That means testing is not identical at all places. Also, it's possible that two different kinds of tests were used to test for HER2. One test may have been a measure of HER2 protein levels ("IHC") and the other test could have looked at the HER2 gene level ("FISH"). Of these two tests, the FISH test is more reliable.

Try to work with your doctors to help sort this out so that your treatment moving forward is best tailored for your situation.

Percentages for hormone receptor status?

Question from Peg: My recent pathology report after lumpectomy stated, "estrogen and progesterone receptors negative." Should I ask for more details (i.e., percentages to get a more specific diagnosis)?

Answers —Ann Ainsworth, M.D.: Estrogen and progesterone receptors are reported as positive or negative. Laboratories establish a cutoff point related to the percentage of cells which stain with the antibody. If the number of cells which stain is greater than that predetermined cutoff point, the result is called positive. If the number is below that number, the result is called negative.

The pathologist may also provide a percentage of cells that are positive for each receptor. Or this percentage may only be given if the cells are at the borderline of what's considered positive or negative, like being 5 to 10 percent positive. This is explained in the pathology report. We think it's best to report both pieces of information: if it's positive or negative, and what percent positive.

Marisa Weiss, M.D., president and founder: If your hormone receptor status is positive, that predicts two things—first, a better overall outcome, and second, a good response to hormonal therapy. The difference in outcome between positive and negative test results is only moderate. The meaning of the test in terms of choosing treatment options is much more important. The higher the percentage of estrogen receptors positive, the greater your chance of responding well to hormonal therapy. The lower the hormone receptor positivity, the better response you'll have to chemotherapy.

Some centers will say the cancer is hormone receptor negative if 10 percent or less of the cells shows receptors. Some centers will use a 5 percent cut-off. Still, cancer with this level of estrogen- receptor positive energy can still have a good response to hormonal therapy.

The important take-home message here is, find out if your estrogen receptor negative result is 0 percent, 5 percent, or 10 percent. If it's 5 to 10 percent, you might want to be able to take advantage of an important type of treatment that could make a difference to you.

Tests to determine growth rate?

Question from Michey: Are the "S-phase fraction" and "Ki-67" tests the only tests to determine how fast the breast cancer is growing? Which procedure do you use and why?

Answers —Beth DuPree, M.D., F.A.C.S.: Currently, my pathology department does not report S-phase or Ki-67 index. This is because we are relying more on the estrogen progesterone receptor, the HER2 status, and the tumor grade.

Marisa Weiss, M.D., president and founder: These two tests of how fast the cancer is growing have limited usefulness when it comes to understanding the nature of the cancer and figuring out the best treatment plan. The tests are good, but they tend to be unreliable, so you can't depend on them too much. There are other ways of figuring out if the tumor is aggressive and fast growing. The tumor grade largely reflects this issue.

The presence of a HER2 abnormality, lymphatic/vascular invasion, lymph node involvement, and absence of hormone receptors all go along with a more aggressive problem. But even if there is an aggressive cancer identified, there are effective treatments that can be used to successfully combat it.

Differing carcinoma diagnoses?

Question from VA Fiend: My surgical pathology report indicates, "invasive mammary carcinoma with lobular features (90 percent) and lobular carcinoma in situ (10 percent)." The core biopsy report says "invasive ductal carcinoma." Are these the same thing, or do the two reports differ?

Answers —Ann Ainsworth, M.D.: Breast carcinomas may originate from the breast ducts that carry the milk or the breast lobules where the milk is made. The cells, which are present in the ducts and lobules, look different under the microscope. Sometimes, however, it is difficult to tell whether the origin of the tumor is ductal or lobular. Sometimes lobular carcinoma and ductal carcinoma can both occur in the same tumor.

In situ lobular carcinoma (also called LCIS and sometimes called lobular neoplasia) means that the tumor cells are present within the lobules where they originated and have not spread to the surrounding breast tissue. This type of cell overgrowth is not truly a cancer, but a marker for future risk of developing breast cancer. Ductal carcinoma in situ (also called DCIS) is a non-invasive cancer which does require treatment.

Beth DuPree, M.D., F.A.C.S.: Clinically, basic lobular carcinoma may present as a ridge or a density in the breast and may not be as easily found on a mammogram as are invasive ductal carcinomas. And because of the pattern of growth within the breast, (it can form an area of generalized thickening rather than a discrete lump), some invasive lobular carcinomas are more difficult to remove completely with breast-conserving surgery (lumpectomy). Patients found to have LCIS without any other form of invasive cancer are treated with close clinical observation. They'd also be candidates for tamoxifen therapy in order to reduce breast cancer risk.

Marisa Weiss, M.D., president and founder: If a woman with a strong family history of breast cancer or a known breast cancer gene abnormality gets LCIS, she may decide to be extra aggressive with her options. Some women in this situation might seriously consider prophylactic mastectomies, to reduce their high risk of getting breast cancer in the future. A woman is at high risk if she has a strong family history of breast cancer (a lot of women affected by breast cancer at a young age, and possibly also having ovarian cancer) or has a proven breast cancer gene abnormality.

Worry about close chest wall margin?

Question from Kitty: I had a lumpectomy that was close to the chest wall. My doctor said he could not have take more out if he had done a mastectomy. Should I worry about the margins? I have invasive breast cancer, grade 3 tumor.

Answers —Beth DuPree, M.D., F.A.C.S.: When we perform breast-conserving surgery, we are only able to remove tissue around the tumor up until the point where we reach the chest wall. (the rib cage behind the breast, that's covered with muscle). We try to do whatever is possible to get clear margins. We also try to leave as much healthy breast tissue intact.

The deep margin, which is up against the muscle of the chest wall, is often our most difficult margin. Once we physically remove the tumor off the chest wall muscle, we have physically removed the largest limit of breast tissue that we can from that area. There is a layer between the muscle and the breast tissue that is called the fascia. This is a flat layer of tissue that separates the breast from the muscles of the chest wall. If the back (also called "posterior") margin was either close or positive, we need to enlist the help of our radiation oncologist. Knowing exactly where the margin is tight, can help the radiation oncologist plan their radiation therapy treatment.

Marisa Weiss, M.D., president and founder: As a radiation oncologist, if the deep margin or posterior margin is positive or very close, I immediately pick up the phone and bug the pathologist. I need her to help me better understand if the tumor went to the back of the breast and stopped there, or if it went into the fascia and/or the muscle. Sometimes it's hard to sort all of these questions out.

I also call the surgeon to learn what I can from her. This week alone I've had 3 patients with a close or positive deep margin. Ultimately, we proceed with radiation, and I aim my boost dose to the area of concern. I also have the ability to go to a higher dose if the margin is clearly positive. If the surgeon is concerned during surgery around the deep margin, she might choose to place tiny metal clips to mark the area where she knows the margin to be close. This gives me a very accurate target to focus my radiation dose on.

Beth DuPree, M.D., F.A.C.S.: This requires teamwork with your health care professionals to make the best treatment plan for the particular cancer with which you've been diagnosed.

What to read before my pathology report?

Question from Hockey Mom: What can I read ahead of time to understand all these terms? Is there a book you can recommend?

Answer —Marisa Weiss, M.D., president and founder: Go to www.breastcancer.org. We have a Celebrity Talking Dictionary, where you can actually hear the words pronounced, and definitions of all the terms. We also have a booklet specifically on "Understanding Your Breast Cancer Pathology Report." You can download a copy on the Web site or order a free copy, in English or in Spanish. Bring this to your doctor's office and ask your doctor to fill in the information that is specific to your case. Only your doctor can tell you how your unique circumstances will influence the design of your treatment plan.

What is lymphatic invasion? Necrosis?

Question from Patty: What is lymphovascular invasion and lymphatic invasion in the tumor? And what is necrosis? My pathology says areas of necrosis are present in the tumor centrally.

Answer —Ann Ainsworth, M.D.: Lymphatic or vascular invasion means that the tumor cells have gotten into the fluid-carrying channels within the breast. Tumors with this kind of invasion are at increased risk for spread beyond the main cancer within the breast, to the lymph nodes, and possibly to other areas of the body.

Necrosis in the tumor means that the cancer cells in that area are dead. The pathologic finding of necrosis suggests a fast-growing cancer. This often happens because the tumor runs out of blood supply in the central portion. Without a blood supply, the tumor cells cannot live. When a tumor is necrotic, it may be difficult or impossible to diagnose on a small biopsy, and an additional sample might need to be taken. Tumor necrosis is often focal (limited to a small area) in the region. There are usually living cancer cells nearby that can be diagnosed as cancer using a microscope.

Significance of signet ring cells?

Question from Judi: My diagnosis was metastatic lobular carcinoma with signet ring cell features. Can you explain the significance of the signet ring cell?

Answers —Ann Ainsworth, M.D.: Signet ring cells occur in many types of tumors. This name was given to them because the cells under the microscope look like a signet ring, with the nucleus pushed over to one side (the stone in the ring) and the remainder of the "ring" forming the cell membrane or boundary of the cell. It is a pattern of growth in tumors in gland-forming tumors.

In the breast, when one sees signet ring cells, one thinks of lobular carcinoma rather than ductal carcinoma. Cancers growing as signet ring cells can sometimes be missed or difficult to diagnose since these cells are small and often inconspicuous in the tissue. One has to look especially carefully at the lymph nodes in the patient with lobular carcinoma because this type of cancer can be difficult to see.

Marisa Weiss, M.D., president and founder: Two things I'd like to add. The presence or absence of signet cells has no real effect on the treatment plan. These cells act enough like other breast cancer cells, so standard treatment decisions are roughly the same.

Second, the word metastatic can be used in different ways to mean different things. But it always sounds very scary. The term may be used to describe the spread of cancer cells from one place to another, nearby (like lymph nodes) or further away (like the lungs). There is a whole system of staging that we use to describe the size of the cancer, whether or not there are lymph nodes involved (and if so, how many), and if there is spread beyond the breast and the nearby lymph nodes.

In your situation, if the cancer has spread to the lymph nodes under the armpits only, that could be stage II or III disease. If there is spread beyond that region to other parts of the body, it's referred to as stage IV, also called "metastatic," and sometimes the term "advanced" is used.

What does histological grade mean?

Question from Janet: What does histological grade mean?

Answers —Ann Ainsworth, M.D.: The grade of a cancer is a measure of how much the tumor looks like the normal tissue from where it originated. A grade 1, or well-differentiated carcinoma, looks very much like the normal, nearby breast tissue. Grade 2, or moderately differentiated carcinoma, looks less like the normal tissue. Grade 3 show very little similarities to the normal breast ducts or lobules. Grade I carcinomas tend to behave better than grade 2 or 3 carcinomas.

Marisa Weiss, M.D., president and founder: Tumor grade is completely different from tumor stage (as described above). Stage is a measure of the extent of the disease, and grade is a measure of the nature of the cancer—its personality.

What does 'classical' lobular mean?

Question from Beth: Please explain a tumor described as "classical" lobular.

Answer —Ann Ainsworth, M.D.: Classical lobular carcinoma arises from the lobules of the breast (the milk-making cells) and invades the breast tissue as single cells in a line (you may see the term "Indian file," in your pathology report, to describe this finding). Invasive duct carcinoma grows as small ducts or groups of cells. Signet cell carcinoma is another form of invasive lobular carcinoma, but it is less common than the classical type. The growth pattern of classical invasive lobular carcinoma is very easy to recognize.

Surgeon removed fascia?

Question from Raven: My surgeon removed the fascia. What does this mean?

Answers —Beth DuPree, M.D., F.A.C.S.: The fascia is the connective tissue of the body, and it lies between the skin and the muscle underneath it. There is fascia on top of the muscle right behind the breast. This layer is often removed during a mastectomy and occasionally during a lumpectomy if the tumor is near the chest wall.

You may want to ask your doctor if the tumor was lying near the chest wall and that's why your fascia was removed. The chest wall is made up of your rib cage along with muscles that lie directly in front, just behind the breasts. Working from the front to the back of your chest, the layers of the chest wall are the skin, the breasts, the fascia, the pectoral muscles, and finally, the rib cage.

Marisa Weiss, M.D., president and founder: As a radiation oncologist, I read the operative notes to learn what the surgeon did during surgery and what she was thinking, because it can reveal important information to help me figure out the area where the cancer was. That's where I'm going to focus my treatment. Again, teamwork is essential in order to get the best care possible. The reports that your doctor generates, such as the operative report and the pathology report, are critical to keeping everyone on the same page and facilitating continuity of care.

Lymph, vascular invasion with positive nodes?

Question from Ashley: Lymph and vascular invasion were lumped together in my path report. Is this an important feature if my lymph nodes were positive? How come some people don't have this, yet have positive lymph nodes?

Answers —Ann Ainsworth, M.D.: Lymphatic or vascular invasion means that the tumor cells have acquired the ability to invade the walls of these channels and may spread to the lymph nodes or beyond. We may see involvement of the lymph or vascular channels in the tissue sections we examine under the microscope, and then again, we may not—but the tumor can still be present in lymph nodes. While we examine many sections of the tumor, there may be areas not looked at under the microscope in which invasion of these channels has occurred.

Marisa Weiss, M.D., president and founder: Clinically, both of those pieces of information can be useful. If there is significant lymphatic/vascular invasion within the breast, that is associated with a higher risk of recurrence in the breasts, as well as a higher risk of having lymph node involvement. Knowing this, we work closely with a surgeon to identify the most effective way to treat the breasts so that we can reduce your risk of recurrence there.

For example, it might mean a re-excision to get around both the main cancer as well as cells in the channels. For a woman who has extensive involvement of these channels, she may require mastectomy followed by radiation, as well as systemic treatment, for example, chemotherapy.

Lymph node information also has a significant impact on your treatment plan. If your sentinel lymph node or nodes are involved, your surgeon may talk to you about the possible role of additional lymph node surgery. This depends on your individual situation. If lymph nodes are involved, your radiation oncologist may add a treatment field that includes the lymph nodes.

Systemic therapy is usually given for anyone with lymph node involvement (as well as women without lymph node involvement but with other features that would indicate an increase risk of cancer cells spread beyond the breast). Systemic means treatment of the whole system or the whole body. This can include treatments like chemotherapy, hormonal therapy (tamoxifen), or aromatase inhibitor or immune therapy like Herceptin.

FISH vs. IHC testing accuracy?

Question from Renee: If you had a 2+ staining on the standard HER2 ("IHC") test, but a subsequent 1+ staining on a repeat test using the FISH test, can you really be certain that your HER2 test is negative?

Answers —Ann Ainsworth, M.D.: HER2 testing can be done using a tissue block and staining it with something that is attracted to the HER2 protein. HER2 testing is also performed by another test called FISH. The FISH test looks for the gene itself. The IHC stain is less reliable at the 2+ level than the FISH test. In our laboratory, if the IHC test results are 0 or 1+, the HER2 is considered to be negative. All 2+ and 3+ IHC test results are automatically sent for FISH testing, because this does a better job at that level of IHC staining and is the most reliable test in that circumstance.

A combination of the IHC and the FISH tests are performed in the laboratory to produce the most reliable and accurate results.

Marisa Weiss, M.D., president and founder: Ultimately, your medical oncologist will depend more on the FISH test for the final answer. The reason why we work so hard to come up with a right answer to the question is it cancer HER2 positive or not is because it can have a significant impact on the choice of treatment.

Help translating pathology report? Paget's?

Question from Nancy: Here are the results of my path report after mastectomy: "2 foci of invasive ductal carcinoma, histologic grade 3/3, nuclear grade 2/3, measuring 0.4 cm and 0.2 cm. Nipple - Paget's disease. Vascular invasion is identified." Could you translate? What should follow?

Answers —Beth DuPree, M.D., F.A.C.S.: In this particular pathology report, there are many things happening at once. Paget's disease is typically diagnosed from changes that we see superficially in the nipple complex that lets us know that there are cancer cells within the ducts below the nipple. What the pathology report specifically tells us is that there are two cancers that were growing at the same time. And although they are graded differently, we use the higher grade cancer which in this case would be 3/3 as our determining guide for further treatment.

The vascular invasion is when cancer cells are found in the small blood vessels inside the breast. It is a associated with an increased risk of recurrence. If this is on your pathology report, your doctor will consider this along with all of the other findings, as the role for further treatment such as radiation, chemotherapy or hormonal therapy is evaluated. In addition, the estrogen and progesterone receptors, and HER2 status should be determined for these tumors, as noted previously in this program.

For those who do not know what Paget's disease looks like, it can begin as a very subtle change in the skin surrounding the nipple and areola complex. It can range from a dry skin appearance to an open sore that gets bloody or produces a clear discharge. This can look like a skin erosion or ulcer.

Marisa Weiss, M.D., president and founder: If we see a patient who has Paget's disease plus other changes by physical exam or mammography that are suspicious for significant extension of cancer, then an MRI scan of the breast may be ordered. That test can help us better understand the extent of the disease in the breast. It can help us figure out if there is spread from the nipple back into the central area of the breast. It can help us know if the other areas are separate or connected. Having the benefit of information like this before deciding on surgery can be useful.

Beth DuPree, M.D., F.A.C.S.: When performing any biopsy of the breast, it is very important that I tell the pathologist in my operative report exactly where the tissue came from in the breast. I also need to describe the orientation of the tissue exactly as I have removed it from the breast. By orientation I mean the three-dimensional place that the tissue was residing in the breast, relative to the front margin (anterior), back margin (posterior), top margin (superior), bottom margin (inferior), inside margin (medial) and outside margin (lateral).

When the pathologist knows what areas may have margins that are close or positive with tumor cells, that helps me to figure out what specific areas may need re-excision after a lumpectomy. In communicating this information, the pathologist can determine the extent of the disease within the ductal system of the breast.