title: Denosumab for treatment of breast cancer bone metastases and beyond.
abstract: BACKGROUND
  Bone metastases develop in approximately 70 - 85% of patients with metastatic breast cancer, are incurable and can result in debilitating skeletal complications. Bone-modifying agents to treat breast cancer bone metastases include bisphosphonates. Denosumab is a humanized monoclonal IgG2 antibody targeting receptor activator of NF-κB ligand (RANKL) and provides an alternative therapy for treatment of breast cancer bone metastases.
  
  
  METHODS
  This review provides an overview on denosumab and the RANKL-RANK pathway. Denosumab pharmacokinetics, pharmacodynamics, efficacy, safety and tolerability are discussed. Based on the review of clinical studies, denosumab is efficacious in the treatment of breast cancer bone metastases. Adverse events rates of denosumab are similar to those for bisphosphonates. Preclinical studies have indicated a role of the RANKL-RANK pathway in non-bone-related mechanisms such as mammary gland development and tumorigenesis.
  
  
  CONCLUSIONS
  Clinical use of denosumab remains limited and its place in therapy will continue to be defined. Clinical questions, such as the optimal duration of therapy, remain unanswered and need to be addressed.
authors.affiliation: Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Nangia
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Ma
authors.forename: Christine M
authors.initials: CM
authors.lastname: Nguyen
authors.forename: Margaret A S
authors.initials: MA
authors.lastname: Mendes
authors.forename: Meghana V
authors.initials: MV
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab; D005260:Female; D006801:Humans; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab