title: Denosumab and the current status of bone-modifying drugs in breast cancer.
abstract: BACKGROUND
  Bone-modifying therapy is a primary research interest in breast cancer. Several features contribute to the importance of the bone environment in the management of breast cancer. Firstly, bone metastases represent the most common site of breast cancer metastases and secondly, the emergence of cancer treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is of increasing concern. Furthermore, concordant with the "seed and soil" theory, agents that alter the bone microenvironment may even prevent tumor cell seeding in bone and limit cancer growth.
  
  
  METHODS
  Medical databases and conference proceedings were searched to identify articles, abstracts and clinical trials that have or are investigating denosumab and bisphosphonates in cancer therapy. Our search included a predefined focus on bone-modifying therapies in early and advanced breast cancer.
  
  
  CONCLUSIONS
  Bisphosphonates (BPs) have an established role both in the prevention and treatment of CTIBL and have been studied in the adjuvant setting for early breast cancer (EBC). Denosumab is a monoclonal antibody directed against RANK ligand and thereby inhibits osteoclastogenesis and bone resportion. It is the newest agent approved for the treatment of postmenopausal osteoporosis and the prevention of skeletal-related events (SRE) in cancer patients with solid tumors and bone metastases. Denosumab has a favorable toxicity profile in comparison to BPs and has the potential to improve cancer outcomes.
  
  
  CONCLUSIONS
  This review examines the existing role of denosumab in the treatment of bone complications of breast cancer and its potential role as adjuvant therapy.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, 02114, USA.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Lee
authors.forename: Michaela J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D010024:Osteoporosis / Q000139:chemically induced / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab