Management of bone metastases in patients with breast cancer: review of bone-modifying therapy, emerging new agents, and future directions

Bone metastases occur in 65-75% of patients with metastatic breast cancer. They are often associated with skeletal-related events (SREs), leading to significant morbidity and decline in quality of life (QoL). Treatment with bone-modifying agents is crucial to decrease the risk of SREs and improve QoL. We used PubMed to review key clinical trials that studied the use of bisphosphonates (BPs) and denosumab for the treatment of osseous metastases in patients with metastatic breast cancer. We also reviewed agents that may have the potential to improve SREs. BPs - including clodronate, pamidronate, ibandronate, and zoledronic acid - as well as denosumab have shown efficacy and safety in the treatment of bone metastases secondary to breast cancer. Oral BPs are mainly used in Europe and other countries while zoledronic acid and denosumab are more commonly used in the United States. Zoledronic acid offers the convenience of a once-every-12-week dose. Denosumab may be superior. It is also associated with less renal toxicity and less acute-phase reactions. BPs and denosumab have shown good results; they are usually continued long-term as a palliative treatment. However, they are unlikely to revert osteolytic lesions. There is an unmet need for improvement of SREs. Bone-forming agents should be seriously considered for this purpose.