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Bisphosphonates in the adjuvant treatment of breast cancer: rationale and clinical data

Michael Gnant

Bisphosphonates are established therapies for bone loss and for the prevention of skeletal-related events from bone metastases. Clinical trials in the early breast cancer setting suggested a potential anticancer role for clodronate a decade ago. Recent data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 and one of the Zometa-Femara Adjuvant Synergy Trials (ZO-FAST) demonstrate that zoledronic acid can significantly improve disease-free survival when administered in the adjuvant setting concomitantly with endocrine therapy for breast cancer in the premenopausal and postmenopausal settings. Moreover, a recent subset analysis of the ongoing AZURE trial in patients with early breast cancer revealed that zoledronic acid can significantly reduce residual invasive tumor size, and improve pathologic complete response, versus neoadjuvant chemotherapy alone. There is a wealth of preclinical data illustrating multiple anticancer mechanisms of action of zoledronic acid that might underlie these clinical effects.