BACKGROUND Anthracyclines are among the most active drugs in the treatment of breast carcinoma and exhibit a steep dose‐response curve in vitro. This trial was performed to determine the efficacy and toxicity of epirubicin in the treatment of patients with advanced breast carcinoma when administered as a single agent in maximal doses. METHODS Patients with chemotherapy‐naïve American Joint Committee on Cancer/International Union Against Cancer Stage IIIB or IV breast carcinoma received epirubicin, 180 mg/m2, intravenously every 3 weeks for a maximum of 8 cycles of therapy. Hematopoietic growth factors and cardioprotective agents were not used routinely. RESULTS Twenty‐seven patients were entered in the study. Although NCI/CTC criteria Grade 4 neutropenia occurred in 96% of patients, epirubicin was administered at 83.1% of the planned dose intensity. The median fall in left ventricular ejection fraction was 10%; clinical cardiac toxicity was observed in 3 patients. Objective responses were observed in 21 patients, including 6 complete responses. CONCLUSIONS High dose epirubicin was found to result in substantial hematologic toxicity but was highly active in the treatment of patients with advanced breast carcinoma. Cancer 2000;88:375–80. © 2000 American Cancer Society.