Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.

Abstract

PURPOSE We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 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] i.v., 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 < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 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 < or = 49 years as well. However, the addition of Tam to AC in women age > or 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.