Understanding and optimizing bone health in breast cancer

Bone is the preferred site of metastasis for breast cancer, and presence of skeletal lesions is associated with significant morbidity and poor prognosis. Skeletal-related effects such as pain, pathologic fractures, spinal compression, and hypercalcemia are frequent consequences of skeletal lesions of breast cancer that have debilitating effects on the patients' quality of life. In addition to direct cancer effects on the skeleton, therapies commonly used to treat patients with breast cancer such as chemotherapy and aromatase inhibitors (AI) result in cancer therapy-induced bone loss (CTIBL) which is associated with increased risk of skeletal complications such as fractures. Bisphosphonates are a class of antiresorptive drugs that are now firmly established as the cornerstone of the management of skeletal-related events due to breast cancer. Other novel bone-targeting agents such as the anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody denosumab are also showing promising activity in the treatment of bone metastasis secondary to breast cancer. Moreover, recent provocative evidence suggests that bisphosphonates might also exhibit antitumor activity via direct and indirect mechanisms. The goal of this review is to summarize the pathophysiology of osteolytic bone lesions secondary to breast cancer, provide clinical evidence of currently available bone-targeted drugs in the treatment of bone metastasis and CTIBL, and explore the antitumor activity of current bone-targeted agents in patients with breast cancer.