Abstract:
Bisphosphonates (BPs) have been used in the standard treatment of osseous metastasis in breast cancer because of their exact curative ability to inhibit the osteoclast-mediated bone destruction and treat the bone metastasis of breast cancer. Over the past few years, however, research findings indicated that BPs might also exhibit direct and indirect antineoplastic activities, thus making its application possible for the adjuvant therapy of breast cancer and prevention of bone metastasis of the cancer. Additionally, the antitumor effects of BPs can directly induce apoptosis and the mechanisms of inhibiting chemotaxis, movement, cell adhesion, and invasion of the tumor cells. Such effects can also induce the mechanism for restraining the cancerous cell adhesion to the bone matrix. The indirect effects of BPs include inhibition of epithelial cell proliferation, angiogenesis, and immunoloregulation. There is also a synergistic interaction between the BPs containing nitrogen and cytotoxic drugs. The indirect mechanisms include suppression of endothelial cell proliferation, inhibition of angiogenesis, and modulation of immunity. These may be the basis of the expanded role of BPs in the adjuvant setting. Clinical data also indicated that BPs played a role in the treatment of bone metastases, reduced the probability of skeletal and visceral metastases, and improved the overall survival in the adjuvant setting. Emerging evidence from large population-based retrospective analyses suggests that BPs might be associated with the reduced risk for breast cancer. However, clinical data with BP therapy are limited, and can only provide con?icting evidence regarding their anticancer effects. Several large randomized clinical trials are currently being conducted using new-generation BP zoledronic acid to prospectively con?rm the antitumor role of BPs in breast cancer. The present review assesses the available preclinical and clinical evidence of the anticancer effect of BPs in treating breast cancer.