Taxanes: optimizing adjuvant chemotherapy for early-stage breast cancer.

Taxanes are among the most widely used chemotherapy agents for advanced breast cancer. Results are now available from 21 trials that randomly allocated nearly 36,000 women with early-stage breast cancer to receive first-generation taxane-based adjuvant chemotherapy versus non-taxane-based adjuvant regimens. Three recent meta-analyses suggest that taxanes are beneficial in the adjuvant setting, irrespective of the patient's age, lymph-node involvement, hormone-receptor expression, and HER2 status. Nevertheless, the optimal role for taxanes in the adjuvant management of early-stage breast cancer remains controversial. We review the results of the first-generation taxane trials and discuss possible explanations for the differences observed in these studies, including variation in the 'strength' of anthracycline therapy in the control arms; suboptimal timing, dosing, or schedule of the taxane regimen; a masking effect of trials that included patients with relatively chemotherapy-insensitive luminal A disease; and decreased representation of the putative taxane-sensitive disease subset. Inclusion criteria for future clinical trials must be revised to account for the molecular heterogeneity of breast cancer and further optimize the role of adjuvant taxane therapy in early-stage disease.