title: Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid.
abstract: OBJECTIVE
  Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials.
  
  
  OBJECTIVE
  To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double-blind, placebo-controlled trials.
  
  
  METHODS
  The Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test.
  
  
  METHODS
  Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT).
  
  
  METHODS
  Hazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group.
  
  
  RESULTS
  There was no significant difference in the rate of breast cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8% (n = 29) in the placebo group and 0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when the data from FIT and HORIZON-PFT were pooled (HR, 1.20 [95% CI, 0.89-1.63]).
  
  
  CONCLUSIONS
  These 2 randomized clinical trials do not support the findings from observational research. Contrary to the results from observational studies, we found that 3 to 4 years of bisphosphonate treatment did not decrease the risk of invasive postmenopausal breast cancer.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00049829 (HORIZON-PFT).
authors.affiliation: San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Trisha F
authors.initials: TF
authors.lastname: Hue
authors.affiliation: San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco2California Pacific Medical Center Research Institute, San Francisco.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.affiliation: Center for Aging and Population Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.affiliation: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.affiliation: San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000517:prevention & control; D018270:Carcinoma, Ductal, Breast; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D015994:Incidence; D007262:Infusions, Intravenous; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D012306:Risk; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D019386:Alendronate
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