Doxorubicin/paclitaxel (Taxol) combinations are very active in advanced breast cancer, with objective response rates up to 90%, but have shown a high incidence of cardiotoxicity. A phase I/II trial replacing doxorubicin with epirubicin (Ellence), a less cardiotoxic analog, produced an objective response rate of 84%, but with a low rate of cardiotoxicity. A careful cardiac monitoring in more than 100 patients treated with this combination has demonstrated that the risk of congestive heart failure is below 10% up to a cumulative epirubicin dose of 990 mg/m2. To examine the possibility that the pharmacokinetic and pharmacodynamic interactions that occur when anthracycline and paclitaxel are administered together might result in subadditive antitumor activity, a phase III study is comparing concomitant vs sequential administration of epirubicin and paclitaxel in patients with advanced breast cancer. A phase I/II study of epirubicin plus docetaxel as first-line chemotherapy for advanced breast cancer patients evaluated the maximum tolerated doses and for subsequent studies recommended epirubicin at 75 mg/m2 plus docetaxel at 80 mg/m2. In the adjuvant setting, an ongoing phase III trial is comparing epirubicin plus paclitaxel vs FEC (fluorouracil, epirubicin, and cyclophosphamide [Cytoxan, Neosar]) in node-positive patients. Preliminary data confirm the cardiac safety of these treatments.