Long-term toxicity of adjuvant regimens is a critical consideration given improvements in survival and consequential management of treatment-related side effects. Despite their well-documented long-term side effects, including a cumulative dose-dependent cardiotoxicity and an increase in the incidence of secondary leukemia, anthracyclines remain an integral component of many adjuvant regimens for breast cancer. The utility of HER-2/TOP2A coamplification in predicting sensitivity to anthracycline chemotherapy has been widely suggested but requires substantiation. The recent maturation of two large phase III trials that directly examined the substitution of a taxane for an anthracycline in the adjuvant setting provides further data to critically evaluate the standard use of anthracyclines in the treatment of early-stage breast cancer. Results from both US Oncology 9735 and BCIRG 006 demonstrated equivalent efficacies in taxane- and anthracycline comparator arms. However, in both trials, the taxane-based regimen(s) resulted in less relative toxicity than the anthracycline-based regimen(s). These trial results pose legitimate questions regarding the future application of anthracyclines in the adjuvant breast cancer setting.
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