Bone-targeted agents and skeletal-related events in breast cancer patients with bone metastases: the state of the art

Most women with advanced breast cancer will develop bone metastases, which are associated with the development of skeletal-related events (SRES) such as pathologic fractures and spinal cord compression. This article reviews the evolving definition and incidence of SRES, the pathophysiology of bone metastases, and the key evidence for the safety an efficacy of the currently available systemic treatment options for preventing and delaying SRES in the setting of breast cancer with bone metastases. The bisphosphonates are structural analogues of endogenous pyrophosphate; three of them (clodronate, pamidronate, and zoledronate) are currently approved for use in Canada in the setting of breast cancer with bone metastases. Denosumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human RANKL (receptor activator of nuclear factor kappa B ligand), thereby preventing osteoclast formation, function, and survival, and reducing cancer-induced destruction of bone. Denosumab has recently been approved in Canada for reducing the risk of SRES from the bone metastases associated with a variety of malignancies, including breast cancer. How to predict the patients that will benefit most from prophylactic treatment, the agents to select and the timing of switches between agents, the dosing schedules and duration. of treatment to choose, the potential utility of the agents in the adjuvant setting, and the utility of additional endpoints such as markers of bone resorption are among the outstanding questions with h respect to the optimal use of anti-resorptive agents for patients with breast cancer and bone metastases.