title: Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.
abstract: Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.
authors.affiliation: Department of Bone Oncology, Endocrinology and Reproductive Medicine, Philipps-University of Marburg, Frankfurt, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hadji
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield r.e.coleman@sheffield.ac.uk.
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield.
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Cancer Centre London, Wimbledon, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.affiliation: INSERM, Research Unit UMR403, University of Lyon, School of Medicine Lyon-Est, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Clézardin
authors.affiliation: Breast Center of the Multidisciplinary Oncology Institute, Genolier, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Aapro
authors.affiliation: Hospital de Santa Maria & Lisbon School of Medicine, Institute of Molecular Biology, Lisbon, Potugal.
authors.forename: L
authors.initials: L
authors.lastname: Costa
authors.affiliation: CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Body
authors.affiliation: Medical School, National University of Athens, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Markopoulos
authors.affiliation: Medical Oncology, University Campus Bio-medico, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.affiliation: Institute for Gynaecological Oncology, Centre for Comprehensive Gynecology, Mannheim, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Diel
authors.affiliation: Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Prato, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: University of Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh.
authors.forename: D
authors.initials: D
authors.lastname: Cameron
authors.affiliation: Institute of Oncology, Bexley Wing, St James Hospital Leeds, Leeds.
authors.forename: D
authors.initials: D
authors.lastname: Dodwell
authors.affiliation: The Royal Marsden Hospital and Institute of Cancer Research, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Smith
authors.affiliation: Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Gnant
authors.affiliation: Clinical Trials and Epidemiological Unit, University of Oxford, Oxford, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.affiliation: Breast Center, Department of Obstetrics and Gynaecology, University of Munich, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: Kantonsspital St Gallen, Breast Center, St Gallen, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Thurlimann
authors.affiliation: Interdisciplinary Breast Cancer Center HELIOS Klinikum Berlin-Buch Germany, Gynecologic Oncology and Obstetrics, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.affiliation: Department of Oncology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Medical Oncology, Institute of Investigation Sanitaria Gregorio Marañón, University Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.affiliation: Department of Bone Oncology, Endocrinology and Reproductive Medicine, Philipps-University of Marburg, Frankfurt, Germany.
authors.forename: U-S
authors.initials: US
authors.lastname: Albert
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: P-F
authors.initials: PF
authors.lastname: Conte
authors.affiliation: Danish Breast Cancer Cooperative Group Statistical Center Department of Oncology Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Karolinska Institute and University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.affiliation: Institute for Obstetrics and Gynaecology, Goethe University, Frankfurt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield.
authors.forename: I
authors.initials: I
authors.lastname: Holen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; 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; D004002:Clodronic Acid / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000517:prevention & control*; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D011795:Surveys and Questionnaires; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid
keywords: adjuvant; bisphosphonates; breast cancer; guidelines