Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy

Caterina Fontanella, Valentina Fanotto, Karim Rihawi, Giuseppe Aprile, Fabio Puglisi

Breast cancer (BC) is the most common female cancer worldwide with approximately 10 % of new cases metastatic at diagnosis and 20-50 % of patients with early BC who will eventually develop metastatic disease. Bone is the most frequent site of colonisation and the development of skeletal metastases depends on a complex multistep process, from dissemination and survival of malignant cells into circulation to the actual homing and metastases formation inside bone. Disseminated tumor cells (DTCs) can be detected in bone marrow in approximately 30 % of BC patients, likely reflecting the presence of minimal residual disease that would eventually account for subsequent metastatic disease. Patients with bone marrow DTCs have poorer overall survival compared with patients without them. Although bone-only metastatic disease seems to have a rather indolent behavior compared to visceral disease, bone metastases can cause severe and debilitating effects, including pain, spinal cord compression, hypercalcemia and pathologic fractures. Delivering an appropriate treatment is therefore paramount and ideally it should require interdisciplinary care. Multiple options are currently available, from bisphosphonates to new drugs targeting RANK ligand and radiotherapy. In this review we describe the mechanisms underlying bone colonization and provide an update on existing systemic and locoregional treatments for bone metastases.