The role of bisphosphonates as adjuvant therapy for breast cancer.

Bone is the most common site of distant recurrence in breast cancer. The development of skeletal metastases involves complex interactions between the cancer cells and the bone microenvironment. The presence of tumor in bone is associated with activation of osteoclasts, resulting in excessive bone resorption. Bisphosphonates are potent inhibitors of osteoclastic bone resorption with proven efficacy in reducing tumor-associated skeletal complications. Several studies have investigated the adjuvant, or preventive, use of these drugs in breast cancer. Laboratory experiments have shown that the development of bone metastases can be inhibited by bisphosphonates. Three randomized clinical trials of bisphosphonates in nonmetastatic breast cancer patients have yielded conflicting results with respect to development of osseous and visceral metastases and survival. Defining the potential role of these agents in adjuvant breast cancer treatment requires further investigation in randomized, large-scale, multicenter clinical trials. The data available to date provide a strong impetus for continued clinical and laboratory work with bisphosphonates in breast cancer.