ADJUVANT RANDOMIZED TRIALS OF DOXORUBICIN CYCLOPHOSPHAMIDE VERSUS DOXORUBICIN CYCLOPHOSPHAMIDE TAMOXIFEN AND CMF CHEMOTHERAPY VERSUS TAMOXIFEN IN WOMEN WITH NODE-POSITIVE BREAST-CANCER

Purpose: We report two randomized trials of adjuvant systemic therapy in 747 patients ≤ 65 years of age with histologically proven node-positive breast cancer. Patients and Methods: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] IV, eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. Results: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women ≤ 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed fol- lowing therapy with CMF compared with Tarn. In patients ≥ 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OS, P = .5). These results must be interpreted cautiously, since a posthoc stratification of patients by age (≤ 49, ≥ 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients ≤ 49 years as well. However, the addition of Tam to AC in women age ≥ 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. Conclusion: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients. © 1993 by American Society of Clinical Oncology.