2ND MALIGNANCIES FOLLOWING CMF-BASED ADJUVANT CHEMOTHERAPY IN RESECTABLE BREAST-CANCER

Background: Only a few studies have evaluated the long-term effects of adjuvant chemotherapy for breast cancer. Furthermore, neither the rel ation between the risk of second malignancies and type of adjuvant reg imen utilized nor the interaction between chemotherapy and breast irra diation or age of the patients have been described in detail. Methods: A total of 2,465 patients entered into prospective studies of CMF-bas ed adjuvant chemotherapy carried out at the Milan Cancer Institute bet ween June 1973 and July 1990 were evaluated. The median follow-up was 12.0 years and detailed information about therapy was available for al l patients. Results: At 15 years, the cumulative actuarial risk of sec ond malignancies (excluding contralateral breast cancer and basal skin cancer) was 6.7% +/- 0.8% for the total series. The figures were 8.4% +/- 2.9% after local-regional treatment alone, 6.4% +/- 0.9% followin g CMF, and 5.1% +/- 1.0% following CMF plus Adriamycin (doxorubicin; F armitalia-Carlo Erba, Milan, Italy). Compared to the general female po pulation, the relative risk following CMF-based adjuvant chemotherapy was 1.29. Three patients, all of whom had received CMF-based chemother apy, developed acute non-lymphocytic leukemia (cumulative risk 0.23% /- 0.15%; relative risk 2.3). No differences were evident when breast irradiation was considered, but the cumulative risk of second tumors w as slightly higher in women aged greater than or equal to 50 years at surgery (7.7% +/- 1.3%) than in younger patients (6.0% +/- 1.0%). Conc lusions: At present, there is no evidence of a significantly increased risk of second malignancies following adjuvant CMF-based chemotherapy such as the one given in this case series. A low risk of acute leukem ia was associated with the cumulative total dose of cyclophosphamide a dministered, and breast irradiation did not enhance this risk. Implica tions: Our findings suggest that there is no reason to omit alkylating agents from short-term effective adjuvant chemotherapy.