title: Denosumab for the treatment of bone metastases in advanced breast cancer.
abstract: In women with advanced breast cancer, approximately three-quarters develop metastases to the bone, with a median survival after diagnosis of 2-3 years. Receptor activator of nuclear factor-κB (RANK) and RANK ligand (RANKL) belong to a signal pathway highly implicated in the development of bone metastases. Denosumab, a human monoclonal antibody with high affinity and specificity for RANKL, prevents the RANKL/RANK interaction and inhibits osteoclast formation and function, thereby decreasing bone resorption and increasing bone mass. Denosumab compared with zoledronic acid showed superior efficacy in delaying time to first-on study SRE and time to first- and subsequent-on study SREs as well as reduction in bone turnover markers. These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer.
authors.affiliation: Medical Oncology Department, Universitary Hospital Virgen del Rocio, Sevilla, Spain. Electronic address: anacasas05@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Casas
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D000069448:Denosumab; D005260:Female; D006801:Humans; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab
keywords: Bisphosphonates; Denosumab; RANK; RANKL; Skeletal-related events