Breast cancer is known to be associated with a high incidence of bone metastases. Recent advances in treatment of breast cancer have improved the prognosis, including in patients with bone metastasis, highlighting the importance of treating bone metastasis to reduce incidence of skeletal complications and improve patients' quality of list (QOL). It has become evident that bone microenvironment such as interaction of cancer cells and osteoclasts or osteoblasts is important for establishment and progression of bone metastases. Bone-targeted therapy that modulates osteoclasts or osteoblasts has been developed recently.
Bisphosphonates (BPs), especially zoledronic acid, decrease skeletal-related events (SRE) and are commonly used for the treatment of bone metastasis. BPs have shown evidences of anti-tumor efficacy in several clinical trials, such as ABCSG-12 and AZURE. However, the outcomes of BP therapy leave room for the improvement with regards to their efficacy, safety and convenience, and other bone-targeted therapies are also being developed.
Many studies have indicated that receptor-activator of NFkappaB ligand (RANKL) plays an important role in bone resorption by osteoclasts. Denosumab is a fully human monoclonal anti-RANKL antibody, which suppresses differentiation, activation, and survival of osteoclasts by inhibiting the binding of RANKL to its receptor, RANK. In a phase III clinical trial, denosumab significantly decreased the time-to-first and time-to-first and subsequent SRE compared with zoledronic acid in advanced breast cancer patients with bone metastases, and denosumab was recently approved for bone lesions of solid cancer and myeloma. Other targeted agents such as SRC inhibitors and c-MET inhibitors are also being developed. Bone metastasis treatment for cancer patients is expected to evolve further with the development of new bone-targeted agents in the near future.