Second malignancies after CMF for resectable breast cancer.

From June 1973 to May 1978, a total of 845 women with resectable breast cancer and positive axillary nodes were entered into two consecutive randomized studies evaluating adjuvant chemotherapy. All patients were subjected to radical or modified radical mastectomy, none received postoperative radiation, and 666 were administered adjuvant CMF (cyclophosphamide, methotrexate, and fluorouracil). After a median follow-up in excess of 10 years, no cases of acute nonlymphocytic leukemia were detected, but 21 second solid tumors other than contralateral breast carcinoma were documented. The cumulative frequency was 4% +/- 1.9% after surgery alone, and 4.2% +/- 1.03% following adjuvant CMF. No differences were observed between patients aged up to 50 years (surgery, 3.1% +/- 2.2%; CMF, 3.3% +/- 1.3%) or older than 50 years (surgery, 4.5% +/- 2.6%; CMF, 5.2% +/- 1.8%). During the same period, a total of 29 contralateral breast carcinomas were documented for a cumulative frequency of 3.7% +/- 1.7% after surgery alone and of 5.2% +/- 1.4% following adjuvant CMF, respectively. We conclude that, at present, there is no evidence for an increased risk of second malignancies following adjuvant CMF as given in this series. Our findings would suggest that second tumors documented so far cannot be entirely ascribed to treatment with adjuvant chemotherapy, but they could be due to a chance association.