513 Background: A number of groups have now reported results of randomised trials of adjuvant zoledronic acid (ZOL) for women with early stage breast cancer. Following an interaction effect observed in the AZURE trial, where postmenopausal women appeared to benefit from ZOL, we performed a meta-analysis, from both publications and presented data, of the most recent results from these trials. We also looked at recently reported large studies of clodronate and ibandronate in older or postmenopausal women to further examine this hypothesis. Methods: DFS data from 8735 women in 7 trials (AZURE, ABCSG-12, ZO-FAST, Z-FAST, EZO-FAST, NSABP-B34, GAIN) that included a randomization to ZOL vs. control or clodronate/ibandronate vs. control were examined. Median follow-up was 5 years. 14% of women experienced a DFS event. The ABCSG-12 study was included since, although it included only premenopausal women, they were all treated with goserelin, effectively rendering them postmenopausal, prior to and during treatment with ZOL. We analysed the subgroup of women aged ≥50 in the NSABP-B34 study in the absence of information on menopausal status, and included only postmenopausal women from the AZURE and GAIN trials. Sensitivity analyses confirmed that exclusion of some older, small, clodronate studies that lacked DFS data, or failed to report by age or menopausal status would be unlikely to alter these findings. Results: For the 5 ZOL studies alone, there was a very substantial and highly significant DFS benefit for ZOL, 2P=.0006, with a hazard ratio of 0.76, and therefore a DFS risk reduction of 24% (95% CI 11%-35%). The results were, in the main, extremely consistent, with the exception of the very small E-ZO-FAST study, which had only 30 events. The risk reduction lessened to 18% (95% CI 8%-26%) when adding in the clodronate and ibandronate studies, but the result remained highly significant (2P=.00075). Conclusions: These meta-analysis results, including more than 8000 women in a range of studies, now provide strong evidence that ZOL is an effective adjuvant treatment for postmenopausal women with early stage breast cancer, and that the treatment benefits are substantial.
Letrozole in the Extended Adjuvant Treatment of Postmenopausal Women with History of Early-Stage Breast Cancer Who Have Completed 5 Years of Adjuvant Tamoxifen