Bone Homeostasis and Breast Cancer: Implications for Complex Therapy and the Maintenance of Bone Integrity

The standard of care in bone metastases is antiresorptive therapy. If present in the bone, tumor cells induce a vicious cycle by stimulating the osteoclasts, which further accelerates tumor progression. The widely-used bisphosphonates or the new therapeutic option, denosumab an inhibitor of the receptor activator of NF-κB ligand (RANKL), interrupt this vicious cycle, inhibit tumor growth, and in clinical practice prevent skeleton-related events. Adjuvant oncological therapy, including chemotherapy and endocrine manipulations (ovarian ablation and tamoxifen in premenopausal, and aromatase inhibitors in postmenopausal women), increases the bone turnover and the risk of fracture. Awareness is essential for the diagnosis and treatment of cancer therapy-induced bone loss, or its prevention with appropriate calcium and vitamin D supplementation. A new possibility has been suggested for the prevention of relapse: the use of bisphosphonates in the adjuvant setting. Three large studies and their meta-analyses indicate that the inhibition of bone remodeling prevents the growth of dormant tumor cells and cancer relapse in the population of postmenopausal patients with a low-estrogen environment in the skeleton. The similar potential of a RANKL inhibitor is currently under evaluation. Since the maintenance of bone integrity is necessary for the prevention of both therapy-related side-effects and progression of the disease, the management of breast cancer at any stage requires a careful consideration of the bone homeostasis.