Bone metastasis of breast cancer

Bone is the most common site of metastasis for breast cancer. Bone metastasis significantly affects both quality of life and survival of the breast cancer patient. Clinically, complications secondary to bone metastasis include pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Because bone metastasis is extremely common in patients with metastatic breast cancer, clinical management of bone metastases is an important and challenging aspect of treatment in the metastatic setting. The skeleton is a metabolically active organ system that undergoes continuous remodeling throughout life. A delicate balance of the bone-forming osteoblasts and bone-resorbing osteoclasts in the dynamic microenvironment of the skeleton maintains normal bone remodeling and integrity. The presence of metastatic lesions in bone disrupts the normal bone microenvironment and upsets the fine balance between the key components. The changes in the bone microenvironment then create a vicious cycle that further promotes bone destruction and tumor progression. Various therapeutic options are available for bone metastases of breast cancer, and treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Commonly used modalities include local therapies such as surgery, radiation therapy and radiofrequency ablation (RFA) together with systemic therapies such as endocrine therapy, chemotherapy, monoclonal antibody-based therapy, bone-enhancing therapy and radioisotope therapy. Despite the use of various therapeutic modalities, bone metastases eventually become resistant to therapy, and disease progresses. In this chapter, we describe the clinical picture and biological mechanism of bone metastases in breast cancer. We also discuss known risk factors as well as detection and assessment of bone metastases. We present therapeutic options for bone metastasis using a multidisciplinary approach. Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies.