title: Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study.
abstract: BACKGROUND
  Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs.
  
  
  METHODS
  PMW with EBC receiving letrozole (2.5 mg/day for 5 years) were randomly assigned to immediate zoledronic acid (ZOL; 4 mg every 6 months) or delayed ZOL (initiated only for fracture or high risk thereof).
  
  
  RESULTS
  Patients (N = 1065) had a median age of 58 years; 54% had received prior adjuvant chemotherapy. At 36 months, mean change in L2-L4 bone mineral density (BMD) was +4.39% for immediate versus -4.9% for delayed ZOL (P < 0.0001). Between-group differences were 5.27% at 12 months, 7.94% at 24 months, and 9.29% at 36 months (P < 0.0001 for all). At 36 months, the immediate-ZOL group had a significant 41% relative risk reduction for disease-free survival (DFS) events (P = 0.0314). Adverse events are consistent with the known safety profiles of the study drugs.
  
  
  CONCLUSIONS
  At 36 months, immediate ZOL was more effective in preserving BMD during letrozole therapy. Immediate versus delayed ZOL led to significantly improved DFS. Benefits are observed in the context of a favorable, well-established safety profile for letrozole and ZOL.
authors.affiliation: Klinik für Gynäkologie und Geburtshilfe, Universitäts Frauenklinik Kiel, Germany. Electronic address: eidtmann@email.uni-kiel.de.
authors.forename: H
authors.initials: H
authors.lastname: Eidtmann
authors.affiliation: Medical Oncology, Royal Melbourne Hospital, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: de Boer
authors.affiliation: South Manchester University Hospital, Academic Surgery, Education and Research Center, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: Bundred
authors.affiliation: Hospital Universitàri Arnau de Vilanova, Lleida, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Llombart-Cussac
authors.affiliation: Broomfield Hospital, Chelmsford, Essex, UK.
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.affiliation: Hospital 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: Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.affiliation: Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
authors.forename: N
authors.initials: N
authors.lastname: Schenk
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, UK.
authors.forename: R
authors.initials: R
authors.lastname: Coleman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D000077289:Letrozole; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole