Chemotherapy for breast cancer – clinical case
I have the following patient who is seeing 2 Oncologists for opinions–the first a general rural Oncologist and the second a bone marrow transplant specialist. I am sure she will ask me for my opinion of their opinions, so I ask your advice.
44 year old white female, normal mammograms 6 years ago, 2 young maternal cousins have had and are surviving breast cancer, 1 slightly older paternal cousin died of breast cancer, no other family hx of breast cancer.
Presented with upper outer quadrant mass (non-distinct about 2 cm by palpation) and diffuse suspicious microcalcifications throughout left breast, normal right breast mammogram.
At biopsy, mass was invasive ductal and intraductal and ca was present at all my biopsy margins (generous biopsy).
Mod rad mastectomy showed another non-palpable focus of cancer in upper inner quadrant separate from primary mass and extensive intraductal and intralobular components, 5 out of 70 nodes positive–all positive nodes were low in axilla (and from visual observation appeared far lateral–assuming that the clinically enlarged nodes were the positive nodes).
I tried to send her to an Oncologist in our closest referral center, but he said that he would not personally treat her, instead he recommended referral to the bone marrow transplant specialist.
What do you think:
- 1) Is the best chemotherapy for her?
- 2) Should she have Radiation Therapy?
- 3) She wants to know whether she should have right mastectomy prophylactically
- 4) Should her daughters have genetic testing, if so, at what age should this start?
You are dealing with a T1c N1 invasive ca; the rest are in situ tumours. Treatment protocols are controversial but the mainstream approach well established to include:
1. Systemic chemotherapy which should improve survival in such as premenopausal patient.
2. Radiation therapy NOT indicated after total or modified radical mastectomy; not to the breast, nor to the axilla.
3. NO.
4. I do not know
5. Bone marrow transplant at this stage?? Is it a joke?
In response to your questions:
1) I prefer the AC containing regimens in young women as long as they are healthy especially in view of several new protocols with high dose chemo being evaluated. On the other hand CMF regimens are still quite good and we don’t have all the answers yet.
2) No XRT is needed unless there is chest wall involvement or extracapsular
extension of the tumor beyond the lymph node capsule.
3)NO
4) Thisis a very common question these days in light of the BrCA1 and 2 genes. There is at least one commercially availablecenter back east (?Maryland). I tend to discourage my patients at this point in time because I believe that it is opening Pandora’s box. We don’t have the best answers for these questions. We don’t have a prevention. We know these women who test positive have somewhere between70 and 90% chance of having the disease in theirlifetime and it starts young. Do we tell a 20 year old to wait and have her be diagnosed with it at 28 and if we test her, do we remove her breasts when we know it really isn’t prophylactic? Too many unanswered questions and these are patients who need a good support system, counselor, etc. This is not even looking at the impact of health insurance and life insurance either. I prefer to teach awareness, exam and vigilance. Good luck.
I am not sure whether the bone marrow transplant specialist will recommend bone marrow transplant–I just thought it was odd that the regular Oncologist said he would not personally treat patient, but would refer her to bone marrow transplant specialist.
I had just discussed with patient how our clinic Oncologist could do her chemo–he has even treated several recurrent breast cancer patients with Taxol and I had just told her that the only thing we could not do locally is bone marrow transplant, which I did not think would be an option unless she relapsed and even then bone marrow transplants in breast cancer have not been shown to help that much.
Her larger tumor is moderately differentiated. Her estrogen and progesterone receptors are positive. Her tumor is aneuploid with high S phase fraction.
No joke. I have sent two patients to be evaluated for a protocol with primary bone marrow transplant being one arm of the study (this was at Duke). It has been a while so I don’t remember the details, but they were both young women with >10 positive lymph nodes.
What is the status of the estrogen and progesterone receptors? Reply to your query:
1) Adriamycin based chemo +/- tamoxifen depending on ER/PR status
2) No need for XRT if margins negative
3) I’m not a fan of prophylactic mastectomy even though her lifetime risk of contralateral CA is high (moslty because of contralateral disease). Good follow up is a better option than more surgery and possible reconstruction.
4) BRAC-1 genetic testing may well be indicated, but stay tuned, BRAC-2 will soon be making headlines
1) Is the best chemotherapy for her?
Cytoxan, Adriamycin, 5-FU is the gold standard (no other regimen proven better) CAF is sometimes followed by pure Adriamycin intensification. There are probably experimental protocols with Taxol, but I would want my wife to get all the CAF she could handle. Probably good in this case to follow with oopherectomy or Tamoxifin. I think bone marrow transplant is only for Stage 3, or >10 nodes (+). I don’t know why the local oncologist won’t treat Stage 2 breast cancer? Has the field become so litiginous that he just wants “hands off” ?
2) Should she have Radiation Therapy?
Well what were the margins like. Was there invasive or extensive intraductal carcinoma at the deep margins of the breast? If there was, then its more like a T3 lesion, and chest wall irradiation is helpful to avoid local recurrence. Avoid the axilla. After a 70 node dissection, lymphedema will be a problem with any RT to the axilla. If the margins were clear then I wouldn’t reccommend it.
3) She wants to know whether she should have right mastectomy
prophylactically
No, I think the horse is out of the barn with the Left breast. She has probably no better than a 50% chance of surviving this cancer, and the likelyhood of a new Ca springing up despite surveillance in the R breast, and metastasizing and killing her when the L cancer didn’t, is remote.
4) Should her daughters have genetic testing, if so, at what age should this
start?
The BRCA-1 gene is a autosomal dominant one, so if her mother and mother’s mother are old and have had no cancer then she didn’t get the gene from them. It could have been hiding in her fathers ancestors but this is probably not likely. I don’t know how difficult it is to get this test. It might be reassuring.
Hey, you do a hell of an axillary dissection, and your pathologists must be “indefatigueable”.
I have never seen 70 LN identified in axillary specimen.
in response to your questions, I have these comments:
CAF or CMF should be given. I don’t think there is any accepted advantage of one over the other, although the trend seems to be towards the Adriamycin based regimens in breast and other malignancies. Taxol is not currently acceptable as a first line agent.
Some radiation oncologists would recommend RT after MRM when there is extracapsular extension in the LN mets. I am not personally completely familiar with that literature, so I can’t comment further.
In terms of prophylactic mastectomy, this a very difficult question today, particularly because of the existence of research-only genetic testing (Oncormed, in Maryland) and the commercial availability by the end of summer, supposedly, of at least a BRCA1 test and possibly a BRCA2 test from Myriad Genetics in Salt Lake City. If you did perform genetic testing on this woman, and I think I probably would, and she is positive, would she then be a better candidate for a prophylactic mastectomy? There is absolutely no data in the literature on this situation, but it has been used in patients with Multiple Endocrine Neoplasias at my institution with great success for the prophylactic treatment of medullary thyroid cancer.
Genetic testing for breast cancer will cause quite an uproar. This weekend, the American Society of Clinical Oncologists is officially releasing their statement on this problem at their annual meeting. The statement text is in the current issue of the Journal of Clinical Oncology. The statement basically says that testing is OK as long as you provide adequate counseling to patients who test positive, and as long as there are ongoing protocols to evaluate the implications of the tests. Unfortunately, the involvement of for-profit, publicly traded companies such as Oncormed and Myriad Genetics, to name two, will push all of us to have to deal with the situation before complete data is available.
In terms of Bone Marrow Transplantation, it is another trend among many oncologists, particularly since autologous stem cell support appears to lessen hospital stays and morbidity, while unfortunately not (yet) impacting on survival.
It’s the Pathologist, not me. I have done the same type of axillary dissection at every hospital I have worked at and some Pathologists have reported as few as 9 axillary nodes, but current Pathologist has found as many as 79 nodes. He is extremely compulsive. One of his recent feats was finding a single microscopic focus of carcinoma in a 3 cm breast cyst, by sectioning entire cyst and looking at every single slide. AFIP decided this was possibly invasive–patient was 82–this created an ethical dilemma. Her surgeon (not me) decided to just observe her.