title: Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in clinical stage II/III breast cancer.
abstract: BACKGROUND
  Despite neoadjuvant/adjuvant chemotherapy, women with resectable stage II/III breast cancer (BC) have high risk of recurrent disease. Recent data suggest that zoledronic acid (ZOL) therapy concurrent with adjuvant treatments may improve cancer-related outcomes in patients with BC.
  
  
  METHODS
  Disease-free survival (DFS; secondary end point) and overall survival (OS; tertiary end point) were evaluated in 119 women with stage II/III BC randomised to intravenous ZOL 4 mg every 3 weeks for 1 year or no ZOL (control) starting with the first chemotherapy cycle.
  
  
  RESULTS
  At 61.9 months' median follow-up, there was no significant difference in recurrence or survival between study arms. However, time to recurrence or death (DFS) was significantly different between subgroups defined by oestrogen receptor (ER) status (interaction P=0.010 for DFS and 0.025 for OS). Hazard ratios (HRs) for disease recurrence and death were significantly less among patients with ER-negative (ER(-)) tumours who received ZOL vs no ZOL (DFS: HR=0.361, 95% confidence interval (CI) 0.148, 0.880; OS: HR=0.375, 95% CI 0.143, 0.985).
  
  
  CONCLUSIONS
  ZOL administered with chemotherapy may improve DFS and OS in a subset of BC patients with ER(-) tumours. This study was not powered to compare subgroups of patients; thus, these findings should be considered hypothesis generating.
authors.affiliation: Department of Surgery, Washington University School of Medicine, Campus Box 8109, 660 South Euclid Avenue, St Louis, MO 63110, USA. aftr@wustl.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Aft
authors.forename: M
authors.initials: M
authors.lastname: Naughton
authors.forename: K
authors.initials: K
authors.lastname: Trinkaus
authors.forename: K
authors.initials: K
authors.lastname: Weilbaecher
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000401:mortality; D011960:Receptors, Estrogen / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D011960:Receptors, Estrogen; D000077211:Zoledronic Acid