Bisphosphonates in breast cancer: clinical activity and implications of preclinical data.

Breast cancer is the most frequently diagnosed and second deadliest cancer among women. Bisphosphonates are stable pyrophosphate analogues used to treat skeletal-related events resulting from bone metastases. In the adjuvant setting, they have been shown to prevent aromatase inhibitor-associated and chemotherapy-induced bone loss. There is a growing body of evidence that bisphosphonates have direct and indirect anticancer activity in the preclinical and clinical settings. These include the inhibition of tumor growth; induction of apoptosis; synergism with chemotherapy; inhibition of tumor migration, invasion, and metastasis; reduction in disseminated tumor cells; inhibition of angiogenesis; stimulation of immune surveillance; and suppression of bone-derived growth factors. In addition to reducing the risk of breast cancer, bisphosphonate therapy has been shown to improve outcomes of early and metastatic breast cancer treatment. This review provides a brief overview of the current role of bisphosphonates in clinical practice and discusses their potential as anticancer agents.