Introduction

The bone microenvironment can provide a fertile "soil" in which metastasizing cancer cells may grow (1). The majority (~70%) of patients with advanced breast cancer develop bone metastases (2), which can have devastating consequences for their quality of life (QoL) and functional independence (3). Metastatic bone disease from breast cancer typically involves the ribs, spine, pelvis, skull, and proximal limbs, and can compromise skeletal integrity (4). Patients with bone metastases have an increased risk of skeletal-related events (SREs), which include pathologic fractures, the requirement for palliative radiotherapy or surgery to bone, spinal cord compression, and hypercalcemia of malignancy (5). In a 2-year, large-scale, randomized clinical trial in patients with bone metastases from breast cancer, SREs occurred in 68% of patients (N = 384) who did not receive bone-specific therapy (Figure 1) (6). Similarly, approximately 50% of patients with bone metastases from breast cancer (N = 113) who received standard anticancer therapy without bisphosphonates experienced an SRE (7). With a median survival in this population of approximately 2 years, patients typically survive long enough to experience multiple SREs from their bone lesions (2,8). For example, in two published reports, patients treated only with standard anticancer therapy experienced 1.1 (7) and 3.7 (6) SREs/year.

Total SREs Pathologic Radiation fractures to bone

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