The effects of anticancer therapies on bone metastases in breast cancer

Breast cancer is the second most commonly diagnosed cancer type and the fourth cause of mortality due to cancer in both sexes worldwide. 5% to 10% of patients have metastatic disease at presentation, and of patients with advanced disease, 65%–75% develop bone metastases, the most common site of distant disease. These carry significant morbidity due to skeletal-related events such as pathological fracture, severe bone pain, spinal cord compression, nerve root compression, and hypercalcemia. In breast cancer patients with metastatic disease, the occurrence of bone metastasis varies with breast cancer subtype. In recent years, major advances have been made in systemic therapies for breast cancer treatment in terms of disease control and survival, including endocrine therapy, CDK4/6 inhibitors, mTOR inhibitors, anti-HER2 drugs, and chemotherapy. Although not specifically bone targeted, these developments have also had major impact on breast cancer patients with bone metastases. This is in addition to the wider use of bone-targeted agents such as potent bisphosphonates and denosumab to reduce the impact of skeletal-related events. New agents for treating metastatic breast cancer continue to be developed. Some of these, while not being specifically bone targeted, may nevertheless have effects on the bones, while others such as cathepsin K inhibitors (e.g., odanacatib), Src inhibitors (dasatinib, saracatinib and bosutinib), radium-223, and anti-TGF-β antibodies are specifically bone targeted