Optimizing adjuvant chemotherapy in early-stage breast cancer.

Mortality in breast cancer has declined in the past decade, owing to advances in diagnosis, surgery, radiotherapy, and systemic treatments. Adjuvant chemotherapy has had a major effect on increasing survival in women with locoregional breast cancer. Like all treatments, adjuvant chemotherapy is a work in progress, and it has evolved from single oral agents to complex multidrug regimens. The choice of regimens is not without controversy, however, and several have been shown to be more effective than others, especially in patients who are at high risk for recurrence. The taxanes paclitaxel and docetaxel (Taxotere) have been shown to be effective in the adjuvant setting, and they have also been shown to improve the outcomes in node-positive disease. Both disease-free and overall survival are greater with doxorubicin, paclitaxel, and cyclophosphamide given in a dose-dense, every-2-week schedule with growth factor support than with the same agents given in an every-3-week schedule. Disease-free and overall survival in patients with node-positive disease are greater with docetaxel, doxorubicin (Adriamycin), and cyclophosphamide (TAC) than with fluorouracil, doxorubicin, and cyclophosphamide (FAC). Febrile neutropenia is common with the TAC regimen, but it can be minimized with growth factor support. Based on these findings, dose-dense therapy and TAC are the current adjuvant treatments of choice in patients with node-positive disease; other, less-intense regimens may be appropriate in patients with lower-risk disease. Ongoing trials are investigating the efficacy of commonly used regimens, new chemotherapeutic and biologic agents, and novel doses and schedules of currently available agents.