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Disease-Free Survival Advantage of Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil in Patients With Node-Negative, Rapidly Proliferating Breast Cancer: A Randomized Multicenter Study

By Dino Amadori, Oriana Nanni, Maurizio Marangolo, Paolo Pacini, Alberto Ravaioli, Andrea Rossi, Angelo Gambi, Giuseppina Catalano, Davide Perroni, Emanuela Scarpi, Donata Casadei Giunchi, Amelia Tienghi, Aldo Becciolini, Annalisa Volpi

From the Department of Oncology, Pierantoni Hospital; Istituto Oncologico Romagnolo, Forlì; Department of Oncology, S Maria delle Croci Hospital, Ravenna; Oncology Day Hospital, Radiotherapy Unit, Careggi Hospital; Department of Clinical Physiopathology, University of Florence, Florence; Department of Oncology, Degli Infermi Hospital, Rimini; Oncology Unit, Bufalini Hospital, Cesena; Oncology Unit, Degli Infermi Hospital, Faenza; Department of Oncology, S. Salvatore Hospital, Pesaro; and Department of Oncology, S Croce e Carle Hospital, Cuneo, Italy.
Deceased.

Address reprint requests to Dino Amadori, MD, Department of Medical Oncology, Pierantoni Hospital, Via Forlanini 34, 47100 Forlì, Italy; email divonco{at}ausl.fo.it or i.o.r@fo.nettuno.it.

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 = .037) 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.

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