Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma - Pooled analysis of 2 consecutive trials

BACKGROUND. The superiority of new generation aromatase inhibitors over tamoxifen in the adjuvant treatment of early breast carcinoma has emerged from several randomized trials. However, until now not all previous studies have shown a mortality benefit. METHODS. A pooled analysis of 2 prospective multicentric trials, sharing the same study design and nearly identical inclusion criteria, was performed. In both trials, women treated previously with tamoxifen for 2 or 3 years were randomly assigned to either continuing tamoxifen for an additional 2 or 3 years or to having their treatment switched to aminoglutethimide or anastrozole for a comparable time period. Mortality was analyzed according to allocated treatment and other patient and tumor variables. RESULTS. In all, 828 postmenopausal women, mostly with estrogen receptor (ER)positive and node-positive tumors who had been monitored for a median time of 78 months (range, 6-141 months) were analyzed. Of these women, 415 were randomly selected to continue tamoxifen and 413 switched to ammoglutethimide or anastrozole. All-cause mortality and breast cancer-specific mortality were significantly improved by the switch: all-cause mortality: hazard ratio (HR) 0.61 (0.420-0.88) P =.007; breast cancer-specific mortality: HR = 0.61 (0.39-0.94) P =.025. No increase was recorded in breast cancer-unrelated mortality in women after switching. Multivariate analysis showed that patient age, tumor size, allocated treatment, and nodal status, in that order, were independent mortality predictors. CONCLUSIONS. Switching to an aromatase inhibitor after 2 or 3 years of tamoxifen therapy significantly improves survival compared with continuing 2 or 3 years of additional tamoxifen treatment. Cancer 2007;109:1060-7. (c) 2007 American Cancer Society.