Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: A randomized multicenter study

Purpose: According to one of the most recent key scientific questions concerning the use of biomarkers in clinical trials, we investigated whether node-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrexate, and fluorouracil (CMF) adjuvant therapy. Patients and Methods: Two hundred eighty-one patients with negative nodes and rapidly proliferating tumors, defined according to thymidine labeling index (TLI), were randomized to receive six cycles of CMF or no further treatment after surgery +/- radiotherapy. Results: The 5-year disease-free survival (DFS) was 83% for patients treated with CMF compared with 72% in the control group (P =.028). Adjuvant treatment reduced both locoregional and distant metastases. When clinical outcome was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was significantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P =.637) and third tertiles (58% v 78%, respectively; P =.024). Conclusion: The results from this randomized clinical study indicate that patients with node-negative, rapidly proliferating tumors significantly benefit from adjuvant CMF. (C) 2000 by American Society of Clinical Oncology.