Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients.

Abstract

PURPOSE The optimal duration and timing of adjuvant chemotherapy for breast cancer patients remain uncertain and were prospectively studied. PATIENTS AND METHODS We randomly assigned 1,554 premenopausal breast cancer patients with node-positive disease in a 2 x 2 factorial design to receive the following: (A) cyclophosphamide, methotrexate, and fluorouracil for 6 consecutive courses on months 1 to 6 (CMF x 6); (B) CMFx6 plus three single courses of reintroduction CMF given on months 9, 12, and 15; (C) CMF for three consecutive courses on months 1 to 3 (CMFx3); or (D) CMFx3 plus three single courses of reintroduction CMF given on months 6, 9, and 12. Accrual was between July 1986 and April 1993. A total of 1,475 patients (95%) were eligible and assessable. The median follow-up duration was 60 months. RESULTS Patients who received CMFx3 without reintroduction had a 5-year disease-free survival (DFS) rate of 53% compared with 58% for the other three treatment groups (hazards ratio [HR], 1.20; 95% confidence interval [CI], 1.00 to 1.45; P = .04). The increased risk of relapse with CMFx3 was more marked for women aged less than 40 years (308 patients; HR, 1.32; 95% CI, 0.94 to 1.84; P = .11) and for patients with estrogen receptor (ER)-negative tumors (455 patients; HR, 1.45; 95% CI, 1.06 to 2.00; P = .02). Reintroduction chemotherapy provided additional benefit (HR, 0.86; 95% CI, 0.73 to 1.01; p = .07), especially for women > or = 40 years of age (1,167 patients; HR, 0.82; 95% CI, 0.68 to 0.99; P = .04). CONCLUSION Three courses of adjuvant CMF chemotherapy are not sufficient compared with longer duration CMF chemotherapy, especially in younger women and in patients with ER-negative primary tumors. Reintroduction chemotherapy showed some evidence of additional benefit, but remains investigational.