In his review of the treatment of breast cancer (Oct. 1 issue), (1) Dr. Hortobagyi discusses the indications for adjuvant treatment. Table 4 of his article shows the selection of adjuvant systemic therapy according to the patient's age, estrogen-receptor status, and "level of risk." The levels of risk are listed as any, low, and moderate or high. How were the levels of risk defined?
Teresa Corcoran, M.D.
Cambridge, MA 02139
Dr. Hortobagyi notes that in women with breast cancer, "The combination of tamoxifen (or ovarian ablation for premenopausal women) and chemotherapy is more effective than either alone." Although this is true for the combination of tamoxifen and chemotherapy, the available data do not indicate that ovarian ablation and chemotherapy are more effective than chemotherapy alone in premenopausal women. In two trials in which surgical oophorectomy and chemotherapy were compared with chemotherapy alone in premenopausal women, the survival rates were similar with the two approaches. (1,2) Furthermore, pooled data from five randomized trials (involving 933 women), including the two trials mentioned above, revealed no differences in terms of both relapse-free survival and overall survival between women receiving chemotherapy plus ovarian ablation and those receiving chemotherapy alone. (3) Therefore, we think ovarian ablation should not be recommended routinely in addition to chemotherapy for premenopausal women with early breast cancer.
Lucia Del Mastro, M.D.
St. Chiara Hospital
56100 Pisa, Italy
Marco Venturini, M.D.
National Cancer Institute
16132 Genoa, Italy
2. Rivken SE, Green S, O'Sullivan J, et al.
Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal,
node-positive, and estrogen receptor-positive breast cancer patients: a
Southwest Oncology Group study. J
Clin Oncol 1996;14:46-51.
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To the Editor:
Dr. Corcoran's question concerns the definition of the level of risk when adjuvant systemic therapy is being selected. I intentionally left the level of risk undefined, because our ability to assess prognosis is evolving. At present, I consider that a woman with breast cancer has a low risk of metastatic disease if her risk is estimated to be around 10 to 20 percent at five years. This level of risk applies to women of any age with primary tumors that are small (1 to 3 cm in diameter), or intermediate or well differentiated, and with no positive axillary lymph nodes. For these women, it is reasonable to consider hormonal therapy or chemotherapy. For women with an individual risk higher than 20 percent, combined therapy is indicated.
Drs. Del Mastro and Venturini are correct in pointing out that there is no strong evidence that the combination of ovarian ablation and chemotherapy is more effective than chemotherapy alone in premenopausal women. This is so to a large extent because of the small number of women in whom the treatments were compared, mostly at a time when information on estrogen-receptor status was not widely available. However, both qualitatively and quantitatively, the trends are in the same direction as for the combination of tamoxifen and chemotherapy. In the Ludwig Breast Cancer Study II, if one restricts the analysis to women with estrogen-receptor-positive tumors, there was a 5 percent absolute improvement in estimated disease-free survival at four years in the combination-therapy group (P=0.12). (1) Furthermore, the report on the meta-analysis of ovarian-ablation trials states, "Among the 550 women with [estrogen-receptor-positive] primary tumors, however, ablation plus chemotherapy appeared to be more effective than chemotherapy alone, both for recurrence-free survival and for overall survival, but these differences were not statistically significant." (2)
There is no plausible hypothesis suggesting that ovarian ablation is inferior to tamoxifen. Although I prefer treatment with tamoxifen to ovarian ablation, the available data strongly suggest that the combination of surgical oophorectomy and chemotherapy is similar in efficacy to the combination of tamoxifen and chemotherapy in premenopausal women.
Gabriel N. Hortobagyi, M.D.
University of Texas M.D. Anderson Cancer Center
Houston, TX 77030