Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of 'cures'

Purpose: To comparatively analyse the risk of recurrence at given times aft er surgery for breast cancer patients receiving or not receiving adjuvant C MF. Patients and methods: A total of 1452 node positive patients, who entered c ontrolled clinical trials carried out at the Milan Cancer Institute and und erwent radical or modified radical mastectomy for operable breast cancer, w ere examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron , hazard rates were fitted by logistic regression models. Results: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18-24 months from surgery (early metastases), a second minor peak at the 5th-6th year, and a tapered plateau-like tail extending o ver 10 years from surgery (late metastases). As expected, the recurrence ri sk of CMF treated patients was lower than the corresponding risk of patient s undergoing surgery only. However, the difference was highly evident for e arly recurrences, while it declined and disappeared afterwards. Conclusion: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable br east cancer has a multipeak pattern. As far as CMF treated patients are con cerned, the unchanged peak timing together with the early recurrence risk r eduction in comparison to controls are much more consistent with the real n onappearance of some early recurrences (putatively 'cured' patients) than w ith the delay in their manifestation. As late relapsing patients seem to ha ve at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases re sulting in late recurrences are required.