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 conce rning the use of biomarkers in clinical trials, we investigated whether nod e-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrex ate, and fluorouracil (CMF) adjuvant therapy. Patients and Methods: Two hundred eighty-one patients with negative nodes a nd rapidly proliferating tumors, defined according to thymidine labeling in dex (TLI), were randomized to receive six cycles of CMF or no further treat ment after surgery +/- radiotherapy. Results: The 5-year disease-free survival (DFS) was 83% for patients treate d with CMF compared with 72% in the control group (P =.028). Adjuvant treat ment reduced both locoregional and distant metastases. When clinical outcom e was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was signif icantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P =.637) and third tertiles (58% v 78%, respecti vely; P =.024). Conclusion: The results from this randomized clinical study indicate that p atients with node-negative, rapidly proliferating tumors significantly bene fit from adjuvant CMF. (C) 2000 by American Society of Clinical Oncology.