Zoledronic acid in the treatment of early-stage breast cancer: is there a final verdict?

Breast cancer, which preferentially metastasizes to bone, is the most common malignancy among women worldwide and is a leading cause of death. Clinical data from large, phase 3 trials (ie, ABCSG-12, ZO-FAST, and AZURE) demonstrate significantly improved disease-free survival with zoledronic acid in some patient populations with early breast cancer. Although the interim results from the AZURE trial did not show a disease-free survival benefit with zoledronic acid in the overall patient population, subset analyses showed that zoledronic acid significantly improved disease-free survival in women with established postmenopausal status at baseline. Similarly, subset analyses of the ABCSG-12 trial showed greater benefits from zoledronic acid in patients over 40 years of age who theoretically would have achieved more complete ovarian suppression. Together, these data support a potential role for zoledronic acid beyond bone health in breast cancer and suggest that the endocrine environment may influence the anticancer potential of zoledronic acid.