Impact of chemotherapy regimens prior to endocrine therapy: Results from the ATAC (Anastrozole and Tamoxifen, Alone or in Combination) trial.

Background: The 33-month median follow-up of the ATAC (anastrozole and tamoxifen, alone or in combination) trial showed a potential interaction between anastrozole and previous chemotherapy; however, this was much smaller at 47 months' median follow-up. When the effects of different chemotherapy regimens were evaluated at that time, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF).

Methods: In this retrospective analysis of 68-month data, we investigated the impact of prior chemotherapy, including different chemotherapy regimens, on time to recurrence. The chemotherapy regimens were 1) CMF only; 2) anthracycline-containing regimens (anthracycline or anthracycline and CMF); and 3) other chemotherapy regimens, including taxane-containing combinations.

Results: No evidence was found for an interaction between prior chemotherapy and anastrozole (hazard ratio [HR] 0.89 vs. 0.74 for those with or without prior chemotherapy, respectively; P = .21 for interaction). For those with prior chemotherapy, the HR of anastrozole when compared with that of tamoxifen shifted from 0.98 (95% confidence intervals [CI], 0.76-1.28) at 47 months' median follow-up to 0.89 (95% CI, 0.71-1.12) at 68 months' median follow-up and was closer to the overall treatment effect (HR, 0.79; 95% CI, 0.70-0.90). No differences according to type of chemotherapy were seen, and a benefit for anastrozole was also now apparent for patients receiving prior CMF (HR, 0.89; 95% CI, 0.63-1.24).

Conclusions: On the basis of the 5-year Completed Treatment Analysis, the ATAC trial does not indicate that the relative treatment benefits of anastrozole differ significantly between patients who received prior chemotherapy and those who did not.