Zoledronic acid in breast cancer: latest findings and interpretations.

The intravenous nitrogen-containing bisphosphonate zoledronic acid has been shown to block multiple steps in tumor metastasis (e.g. angiogenesis, invasion, adhesion, proliferation) in preclinical and translational studies. Moreover, clinical data from the ABCSG-12 and ZO-FAST trials demonstrate significantly improved disease-free survival with zoledronic acid in the adjuvant breast cancer setting. In contrast to these two trials, recent interim results from the AZURE trial do not show a benefit from adding zoledronic acid to adjuvant therapy in the overall patient population. However, subset analyses of AZURE data show that zoledronic acid significantly improved overall survival in women who were more than 5 years postmenopausal or older than 60 years at baseline. Similarly, subset analyses of the ABCSG-12 trial data demonstrate greater benefits from zoledronic acid treatment in patients who theoretically would have achieved more complete ovarian suppression. These observations, together with the AZURE postmenopausal data, suggest that the endocrine environment may affect the potential anticancer activity of zoledronic acid. Indeed, current data support the possibility that zoledronic acid might be most effective for improving disease-free survival in the adjuvant breast cancer setting in women who are postmenopausal or have endocrine therapy-induced menopause.