RANDOMIZED COOPERATIVE STUDY OF PERIOPERATIVE CHEMOTHERAPY IN BREAST-CANCER

Purpose: The aim of this multicentric randomized trial was to determin e whether reducing the interval between surgery and chemotherapy impro ves the outcome of breast cancer patients. Patients and Methods: Betwe en June 1985 and July 1992, 600 breast cancer patients, clinical stage s T1-3A, N0-2, M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m(2), epidoxorubicin 60 mg/m(2), and fluor ouracil 600 mg/m(2) (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophos phamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/ m(2) (CMF). In addition, N+ patients received concomitant or sequentia l 5-year tamoxifen therapy. Results: At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of bord erline significance in relapse-free survival (RFS; 76% v 70%, P = .053 ) was evident. A significant survival advantage for the PC arm was det ected only in the estrogen receptor negative (ER-) patients (P = .003) . RFS was significantly improved in N- patients, postmenopausal patien ts, and ER- patients. Multivariate analyses show that pathologic tumor sire, nodal status, receptor status, and treatment (only in ER- patie nts) are significantly correlated with survival and RFS. PC toxicity d id not influence wound healing. Conclusion: This study provides prelim inary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients. (C) 1995 by American Society of Clinical Oncology.