Women randomized to ovarian function suppression + endocrine therapy + zoledronic acid in the ABCSG (Australian Breast and Colorectal Cancer Study Group)-12 study had a 28% lower risk of recurrence and a 37% lower risk of death at 84 months than women randomized to adjuvant endocrine therapy alone, according to a report by Dr. Gnant, professor of surgery at the Medical University of Vienna. The results of this study confirm data previously reported by the ABCSG-12 investigators showing disease-free survival and overall survival benefits associated with treatment regimens at 48 and 62 months of follow-up (Lancet Oncol. 2011;12:631-41). This 4-group open trial randomly assigned 1,803 female patients to the ovarian suppression + endocrine therapy ± zoledronic acid treatment group for 3 years. Disease-free survival and overall survival were assessed using log-rank tests (log-rank tests) and Cox models. All patients had a mean age of 44.5 years, were premenopausal women, and had undergone surgery for stage I or stage II hormone receptor-positive breast cancer. Patients received goserelin 3.6 mg subcutaneously once every 28 d for 3 years and were randomized to receive oral tamoxifen 20 mg + placebo once daily, oral anastrozole 1 mg + placebo, oral tamoxifen 20 mg once daily + intravenous zoledronic acid 4 mg once every 6 months, or oral anastrozole 1 mg once daily + intravenous zoledronic acid 4 mg once every 6 months. The results showed that at a median follow-up of 84 months, the risk rates of breast cancer recurrence and death in female patients receiving adjuvant zoledronic acid were 0.72 and 0.63, respectively, and the risk reduction remained statistically significant in both univariate and multivariate analyses. In multivariate analyses, “there was no interaction between zoledronic acid and tumor parameters or endocrine therapy.” “Risk rates were the same for small and large tumors, lymph node positive and lymph node negative tumors, and for patients treated with anastrozole and tamoxifen.” For survival benefit, there was a strong interaction between zoledronic acid and age, with a 34% reduction in the risk of recurrence and a 44% reduction in mortality in patients aged >40 years. A similar statistically significant survival benefit was not seen in patients aged <40 years. As expected, arthralgia occurred more frequently in patients treated with zoledronic acid, "but there were no cases of osteonecrosis of the jaw or renal failure in the treated population." The investigators concluded that additional zoledronic acid treatment on top of goserelin and tamoxifen or anastrozole is of great clinical value in the premenopausal with early endocrine receptor-positive breast cancer population, and the results of the ABCSG-12 study provide first-tier evidence for this conclusion. "The continued benefit of this treatment means that we can intervene early and continue to observe treatment benefit."