The evolving role of bone-conserving therapy in patients with breast cancer.

Patients with breast cancer (BC) experience bone loss as a result of either cancer treatment or metastatic disease to the bone. In addition, baseline factors universally associated with bone loss have been identified, including history of fracture, menopausal status, oral corticosteroid use, osteoporosis, and smoking. Whereas treatment effects causing suppression of estrogen function or estrogen-deprivation are the predominant cause of bone loss and fractures among patients with earlier-stage disease, metastatic lesions to the bone are the principal drivers of bone loss and associated skeletal complications in patients with advanced disease. Development of fractures and other skeletal-related events (SREs) is associated with adverse clinical outcome. Several studies clearly have demonstrated the efficacy of bisphosphonates (BPs) in the metastatic setting. Recently, the targeted agent denosumab also demonstrated favorable efficacy in preventing SREs in this setting. In addition, clinical evidence has demonstrated that zoledronic acid (ZOL) can prevent bone loss and may provide an anticancer benefit in earlier-stage breast disease, supporting the potential use of early/concomitant intervention with BP therapy in the adjuvant setting. Overall, these data warrant further consideration of the role of bisphosphonates in BC. Ongoing studies will further investigate the bone-protective and potential anticancer benefits of BPs across all stages of breast disease.