title: Denosumab in breast cancer treatment.
abstract: The bone is the most common site to which breast cancer metastasises. Recently, denosumab, a fully human monoclonal antibody that binds to receptor activator of nuclear factor kappa-B ligand (RANKL) has been developed as a new targeted bone therapy. In a large randomized phase III study with a head-to-head comparison of denosumab to zoledronic acid in patients with bone metastases of breast cancer, denosumab significantly delayed the time to first skeletal related event. In the adjuvant setting denosumab significantly increased bone mineral density compared to placebo in a phase III study in patients treated with aromatase inhibitors. Preclinical data suggest an effect of denosumab on tumour growth and even on carcinogenesis. This review describes the current indications for denosumab in the various settings of breast cancer treatment, with special attention for efficacy, short and long term toxicity and other relevant issues for clinical practice. Furthermore possible and necessary future research questions are proposed.
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands. Electronic address: j.drooger@erasmusmc.nl.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Drooger
authors.forename: Annemieke
authors.initials: A
authors.lastname: van der Padt
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069448:Denosumab; D006801:Humans; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab
keywords: Bone metastasis; Breast cancer; Denosumab