title: Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results.
abstract: BACKGROUND
  Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk.
  
  
  METHODS
  Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points.
  
  
  RESULTS
  At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334).
  
  
  CONCLUSIONS
  Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340.
authors.affiliation: Academic Unit of Clinical Oncology, CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK. Electronic address: r.e.coleman@sheffield.ac.uk.
authors.forename: R
authors.initials: R
authors.lastname: Coleman
authors.affiliation: Department of Medical Oncology, Royal Melbourne and Western Hospitals, Melbourne, Australia.
authors.forename: R
authors.initials: R
authors.lastname: de Boer
authors.affiliation: Clinic for Gynecology and Obstetrics, Universitäts-Frauenklinik Kiel, Kiel, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Eidtmann
authors.affiliation: Medical Oncology Service, Institute Oncologica, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Llombart
authors.affiliation: Cancer Services Directorate, Broomfield Hospital, Chelmsford, Essex, UK.
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.affiliation: Department of Gynecological Oncology, Breast Clinic, UZ Gasthuisberg, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Neven
authors.affiliation: German Breast Group, Frankfurt, Germany.
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
authors.affiliation: Department of Internal Medicine, Haga Hospital, Den Haag, The Netherlands.
authors.forename: H P
authors.initials: HP
authors.lastname: Sleeboom
authors.affiliation: Faculty of Health, School of Medical Practice and Population Health, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Forbes
authors.affiliation: Faculty of Medicine, PUCRS School of Medicine, Porto Alegre, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Barrios
authors.affiliation: Clinical Oncology Unit, St. Anna University Hospital, Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Frassoldati
authors.affiliation: Department of General Surgery, Waikato Hospital, Breast Care Center, Hamilton, New Zealand.
authors.forename: I
authors.initials: I
authors.lastname: Campbell
authors.affiliation: Department of Medical Oncology, Turku University Central Hospital, Turku, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Paija
authors.affiliation: Novartis Oncology, East Hanover, New Jersey, USA.
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.affiliation: Novartis Oncology, East Hanover, New Jersey, USA.
authors.forename: A
authors.initials: A
authors.lastname: Modi
authors.affiliation: Department of Academic Surgery, South Manchester University Hospital, Education and Research Center, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: Bundred
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077289:Letrozole; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole