Two hundred twenty-two patients with stage II or III breast cancer were treated in the first adjuvant trial from M.D. Anderson Hospital. At a median follow-up of 133 months, estimated 10-year disease-free survival was 58 and 36% for stage II and III disease, respectively. Estimated 10-year survival was 62% for patients with stage II disease and 40% for those with stage III disease. The fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC) regimen was effective in improving disease and overall survival regardless of age of the patient, stage of disease, or extent of nodal involvement in comparison with the historical control patients treated with similar local therapy. The treatment was not associated with increased risk of other malignancies, and doxorubicin-related cardiotoxicity was observed in 1% of patients. Long-term follow-up of this study confirms the earlier observation that the FAC regimen is effective in reducing the risk of recurrence and prolonging the survival of high-risk patients.