Dr Love: Debu, How often do you see axillary node recurrence in a woman who’s had axillary node dissection?

Dr Tripathy: In the published literature, we see axillary node recurrence in five to ten percent of women who have had axillary node dissection. There are obviously different determinants in the risk, such as number of involved axillary nodes, grade of the tumor, etc. In the Canadian study of postmastectomy radiation, local recurrence rates were 35 to 40 percent.

As Dr Seidman pointed out, brachial plexopathy and axillary recurrence, especially with lymphedema, is a very challenging clinical problem. I would rely on systemic chemotherapy in the palliative setting, very similar to the way you would treat someone with, for example, symptomatic pulmonary metastases. As we hear more about this case, it sounds unlikely that the patient will be a surgical candidate. The changes in her arm and the possibility of lymphedema and brachial plexus involvement are concerns.

I disagree with the use of radiation therapy in this case. This patient probably received 5,000 cGy. It’s hard to conceive that an additional 2,000 cGy, which would be the absolute most you could deliver, would help much. In fact, causing an iatrogenic brachial plexopathy and lymphedema is more likely. I think we’re left with palliative chemotherapy as our main option.

Dr Love: Dr Argawal, what did you decide to do?

Dr Argawal: I gave her four cycles of carboplatin and docetaxel, and she had an excellent response — actually, I was amazed. The response was so good that she didn’t want to come for the second cycle — her daughter convinced her to continue. The mass was much smaller, the node was smaller and the swelling in her arm had almost completely resolved.

After four cycles of chemotherapy, the surgeon was able to perform a mastectomy with a part of the pectoral muscle dissected, completely resecting the mass. Six of lymph nodes out of seven were positive.

She is now completely healed and there is no evidence of disease. She will also receive additional radiation.

Dr Seidman: If she is very motivated, she could enter a vaccine clinical trial. Otherwise, I don’t believe there is anything else you should be doing for her. I would not continue the chemotherapy because we lack evidence of its benefit, and the only thing we can be certain of is additional toxicity in this scenario.

Case follow-up:
•	Patient received carboplatin and docetaxel weekly (3 weeks on, 1 week off) x 4; tolerated chemotherapy well but had several treatment delays due to grade III and IV hematological toxicity
•	Excellent response; beginning after the first cycle, mass and lymph nodes smaller on physical exam and CT (Figure 1b); arm swelling resolved
•	Underwent a mastectomy, partial resection of pectoralis muscle and axillary node dissection (6/7 nodes positive); recovered well with no evidence of disease
•	Will receive additional infraclavicular and axillary radiation

Dr Tripathy: This patient is technically NED. You could argue that the likelihood of recurrence is so high that an additional two cycles of chemotherapy might delay that recurrence, but it’s hard to believe this would improve long-term outcome and survivability. This patient has completed local therapy and has negative margins. I would probably stop at this point.

Radiation will probably lower the risk of local recurrence, but the trade-off will be a fair amount of toxicity, especially with taxanes and I would be concerned about radiation recall phenomena. Careful shielding and careful attention to detail in port planning is essential if the patient is going to undergo radiation.

Dr Brooks: How would you follow a patient like this? My experience is that physical examination is not very sensitive after these salvage surgical procedures in the infraclavicular and axillary regions.

Dr Seidman: I agree, but I would add that routine imaging studies to detect subpalpable disease radiographically will probably not change the ultimate outcome for the patient. So, from a cost-effectiveness standpoint, physical examination and imaging directed by physical examinations and by symptoms would be indicated.

Dr Brooks: I disagree. I am a proponent of using tumor markers. I would also use CT scans. I favor the imaging approach because of the availability of more tolerable chemotherapeutic agents, such as capecitabine, which almost deserves its own class. I wouldn’t give her multi-agent chemotherapy based on a CT scan finding, but I believe that you can intervene early with capecitabine in a case like this. I think that you can treat an ER/PR-negative cancer with capecitabine early on with a good conscience.

Dr Seidman: In a patient like this with a very high risk of tumor recurrence — particularly if I knew she had elevated markers at the time of her six-centimeter mass — I, too, would keep my antenna up by following tumor markers to intervene early.

Dr Love: Dr Argawal, did this patient have tumor markers checked?

Dr Argawal: No, I didn’t follow tumor markers.

Dr Love: Dr Seidman, if, for example, this woman’s CA 27.29 was very elevated, then dropped down by a quantum amount after the carboplatin/docetaxel, and dropped down further after surgery but was still elevated, what would you do?

Dr Seidman: I would reiterate Dr Brooks’ comments about capecitabine. I would not treat a patient with rising tumor markers with any cytotoxic chemotherapy agent other than capecitabine. I would have a discussion with the patient about the watch-and-wait approach — beginning therapy at the onset of symptoms as opposed to the onset of a rise in biochemical markers. But having said that, once you open the box, it’s hard to close it.

Dr Tripathy: I agree with Dr. Argawal’s approach. I would not check tumor markers in the first place. I don’t know of any reason to use markers, because it’s not clear that initiating therapy based on marker elevations helps patients’ outcomes in the long term.

I don’t want to be absolute about it. The fact of the matter is that I actually have this discussion with patients. I tend to sway them away from using markers, but I do tell them that there are very rare potential scenarios in which one, in retrospect, might say, “I wish I’d used a marker.” For example, in a patient who develops a fairly rapid complication, such as a tumor-related brachial plexus problem, by the time you start them on chemotherapy you cannot alleviate symptoms. You might have saved, or at least delayed, the onset of that problem.

The risk of using tumor markers in this type of situation is that we might over-react. We take a patient who perhaps didn’t need to be exposed to the side effects of chemotherapy for quite some time, and expose them much earlier because of elevated serum markers, but we don’t affect their overall clinical course or their survival. The serum marker problem can cut both ways in terms of helping you or hurting you.

Dr Love: If you believe that adjuvant systemic therapy increases survival by treating micrometastatic disease, why would you not believe that treating Stage IV NED — particularly when you have an in vivo demonstration of active chemotherapy agents — might give her a chance of surviving?

Dr Tripathy: If we had more effective drugs, it’s quite possible that a rising serum marker, or even a positive PET scan might actually result in an improvement in outcome. In fact, we know that is the case in lymphoma and testicular cancer. However, in breast cancer we don’t have good enough agents to do that at this point.

The second point is that two Italian studies have looked at serum markers, and there was no difference in outcome between patients who had them checked versus those who did not. The markers did predict in which patients cancer was going to recur. A serially rising serum marker is associated with an 80 percent likelihood of developing metastases. However, in some cases, these metastases do not develop radiographically for two or three years. So you have a patient in limbo, and you can’t do anything. At this point, there’s no evidence that rising serum markers can help you treat a patient. They are predictive, and that’s why the FDA approved them, but they just don’t help with patient management.

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