title: Breast-cancer adjuvant therapy with zoledronic acid.
abstract: BACKGROUND
  Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients.
  
  
  METHODS
  In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed.
  
  
  RESULTS
  At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups.
  
  
  CONCLUSIONS
  These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).
authors: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, United Kingdom. r.e.coleman@sheffield.ac.uk
authors: Robert E
authors: RE
authors: Coleman
authors: Helen
authors: H
authors: Marshall
authors: David
authors: D
authors: Cameron
authors: David
authors: D
authors: Dodwell
authors: Roger
authors: R
authors: Burkinshaw
authors: Maccon
authors: M
authors: Keane
authors: Miguel
authors: M
authors: Gil
authors: Stephen J
authors: SJ
authors: Houston
authors: Robert J
authors: RJ
authors: Grieve
authors: Peter J
authors: PJ
authors: Barrett-Lee
authors: Diana
authors: D
authors: Ritchie
authors: Julia
authors: J
authors: Pugh
authors: Claire
authors: C
authors: Gaunt
authors: Una
authors: U
authors: Rea
authors: Jennifer
authors: J
authors: Peterson
authors: Claire
authors: C
authors: Davies
authors: Victoria
authors: V
authors: Hiley
authors: Walter
authors: W
authors: Gregory
authors: Richard
authors: R
authors: Bell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles; D053208:Kaplan-Meier Estimate; D010020:Osteonecrosis / Q000139:chemically induced; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid