Bisphosphonates in breast cancer: antitumor effects.

Bone metastases add to the burden of breast cancer, with patients experiencing severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Nitrogen-containing bisphosphonates have become the standard treatment for skeletal-related events and bone pain, as well as for bone loss associated with chemotherapy and aromatase inhibitors. Emerging preclinical and clinical evidence indicates that bisphosphonates negatively affect multiple processes that support tumor growth and proliferation and formation of metastases. Several small clinical trials suggest that bisphosphonates can modify angiogenic factors, immune surveillance, and disseminated tumor cells detected in bone marrow. Emerging data suggest that bisphosphonates used for osteoporosis prevention may inhibit breast cancer development. Three large prospective studies have shown improved outcomes with the addition of zoledronic acid to conventional neoadjuvant or adjuvant therapy. This article focuses on current clinical trials examining the use of bisphosphonates in patients with breast cancer.