Optimizing the use of anthracyclines in the adjuvant treatment of early-stage breast cancer.

Anthracyclines have been incorporated into adjuvant chemotherapy regimens for breast cancer since the 1980s. A metaanalysis confirmed that regimens containing anthracyclines result in better disease-free and overall survival than standard CMF (cyclophosphamide/methotrexate/5-fluorouracil), with a proportional reduction of 11% in risk of death at 10 years with the addition of these agents. Dose escalation of doxorubicin results in outcome improvement up to a threshold dose beyond which no further improvement is seen. Epirubicin, with its better toxicity profile, can be escalated to higher doses than doxorubicin, with better outcomes associated with higher dose levels. Tumors expressing HER2/neu may respond better to anthracycline-containing regimens than to standard CMF, but this remains controversial. Newer regimens combining anthracyclines with taxanes may offer a slight additional advantage in terms of disease-free and overall survival in some patient populations. The scheduling of treatment is important, with recent results of dose-dense scheduling showing a greater survival benefit than conventional scheduling. Ongoing clinical trials should further define the best choice of anthracycline and the optimal dose and schedule of treatment.