Adjuvant Systemic Therapy

21.A. 40-year-old premenopausal woman
21.B. 60-year-old woman
has lumpectomy, axillary node dissection for a 0.8 centimeter poorly differentiated infiltrating ductal carcinoma with one centimeter margins. Tumor is node-negative, ER/PR+. Patient is scheduled for radiation therapy. Your suggested additional management:

Andrew Seidman, MD

Case A.
We shouldn't lose sight of the fact that patients with sub-centimeter breast cancers are likely going to be cured from their local therapy. We have searched high and low over the years to find a poor prognostic subset of these women who have particularly bad-acting breast cancer. Here, the histologic grade is of some concern, but still size is the most important of the prognostic factors available to us in this case. I would feel entirely comfortable with merely an antiestrogen approach. The addition of an LHRH analog in a woman who is still menstruating to tamoxifen is one that certainly is being examined very carefully. But I would not feel at all uncomfortable using tamoxifen in this woman as monotherapy.

I would probably present my bias against chemotherapy. Often the case is that patients will bring in a list of their HER2-neu, Cathepsin, S-phase, and then that'll be a 45-minute discussion regarding the meaningfulness of some of these other prognostic factors. There are people who certainly would point to S-phase as being a meaningful factor, and HER2-neu gene amplification as being a factor that might separate out a subset of women who are at a particularly high risk of relapse. And I have to admit, I am occasionally influenced by some of these factors in the sub-centimeter category, particularly when the patient is ER/PR - negative.

But here we have the option of intervening in a meaningful way without chemotherapy. I'm not going to defend the 60 percent that responded, "We would give this woman chemotherapy."

We had some information from the overview meta-analysis that the proportional reduction in recurrence and death for a premenopausal woman on tamoxifen seems to be similar to that for postmenopausal women. It's just a new enough concept that tamoxifen alone can be effective adjuvant therapy for a premenopausal woman. I think that reflects the difference in audience response based on the patient's age.

Case B.
I agree with the majority here that tamoxifen was appropriate, and we need to factor in the fact that this woman has a small node-negative breast cancer, and she's already highly likely to be cured just from having effective local management.

Clearly, tamoxifen is appropriate. The benefits of chemotherapy are clearly going to be marginal, given that her risk is marginal, and the proportional reduction in the annual odds of recurrence and death is small in postmenopausal women.

22. 40-year-old premenopausal woman has lumpectomy, axillary node dissection for a 1.8 centimeter well-differentiated infiltrating ductal carcinoma with one centimeter margins. Tumor is node-negative, ER/PR+. Patient is scheduled for radiation therapy. Your suggested additional management:

Andrew Seidman, MD

This puts her into a risk category where I think the contribution of chemotherapy to tamoxifen is worthwhile. And I would treat this woman as two-thirds of the respondents would, and that's with chemotherapy as well as tamoxifen. It would be either CMF or AC.

23. 38-year-old woman, ER+, five positive nodes, six months of doxorubicin-based chemotherapy and is continuing to menstruate. She prefers not to receive tamoxifen. Would you offer ovarian ablation?

Andrew Seidman, MD

Despite chemotherapy, this patient still has a significant residual risk of distant metastases. There's clearly a role for an anti-estrogen maneuver here, but if she had no plans to begin tamoxifen, ovarian ablation would be entirely appropriate. I would probably stress to this woman that, of those two maneuvers, tamoxifen is the one associated with the least potential morbidity.

24. How many of your patients have received high-dose adjuvant chemotherapy/SCS in the last nine months?

Andrew Seidman, MD

I'm surprised that 20 percent of respondents did have patients who received high-dose adjuvant chemotherapy, requiring stem cell support, within the last nine months. That number actually seems high to me on the heels of the 1999 ASCO meeting, where there was really no clear prospective data showing benefit. We certainly don't do it outside the context of a clinical trial.

25. Should tamoxifen generally be offered to . . . A. patients with DCIS? B. breast cancer survivors?

Andrew Seidman, MD

Case A.
The answer is yes, because it's something that needs to be discussed with all patients. Based on the NSABP B-24 data, this is something that we know will reduce the incidence of invasive breast cancer and subsequent DCIS. So, it clearly needs to be part of the discussion for any patient with DCIS.

Case B.
I think this is certainly something that's reasonable to discuss with patients, because of the chemopreventive potential. Clearly, there are women whose family histories and own personal history of invasive breast cancer would make me think of this —for example, a woman who had estrogen receptor-negative breast cancer whose family history is compelling. Another group are women who had invasive breast cancer and other pre- malignant histology at the time of their breast surgery or subsequently have had additional procedures where they've had atypical hyperplasia, LCIS, DCIS. And there are many of those women who have lesions other than their invasive lesions.

26. Should HER2 status be considered in . . .
A. deciding whether or not to use tamoxifen?
B. selecting a chemotherapeutic regimen?

Andrew Seidman, MD

I have developed a bias toward including an anthracycline for those tumors that are either HER2neu over-expressing or amplifying. CMF still has a place for tumors that are non-over-expressing. I agree with the majority that HER2neu status should not affect the use of tamoxifen.

27. 62-year-old woman with a history of deep vein thrombosis with a 1.8 cm infiltrating ductal ER/PR+ carcinoma with two positive nodes. Would you discuss the option of receiving an aromatase inhibitor?

Andrew Seidman, MD

In the very near future we're going to have a firm sense of the effect of aromatase inhibitors in the adjuvant setting —either alone or perhaps in combination with SERMS. I can also foresee a time in the future where aromatase inhibitors may be part of an optimal chemopreventive strategy. But we need to be driven by data and not by instinct. Having said that, we all confront patients like this one who require adjuvant hormonal therapy but cannot receive tamoxifen, and the most frequent reason is the issue of thromboembolic phenomena. My understanding is thromboembolic risk is lower with aromatase inhibitors than tamoxifen, and I have no difficulty in offering an aromatase inhibitor as adjuvant therapy in this type of situation.

(Top of Page)

(Back to Contents)