title: Associations between diabetes medication use and risk of second breast cancer events and mortality.
abstract: OBJECTIVE
  Diabetes and certain diabetes medications have been shown to influence breast cancer (BC) risk. Less is known about their relation to BC outcomes. Our objective was to evaluate the effects of diabetes and diabetes medications on risk of second breast cancer events (SBCE) and mortality.
  
  
  METHODS
  This population-based cohort study was conducted among women diagnosed with early-stage (I-II) BC and enrolled in an integrated health plan. Exposures of interest were diabetes and medication classes including insulin, metformin, and sulfonylureas. Outcomes of interest were SBCE defined as recurrence or second primary BC, BC-specific mortality, and all-cause mortality. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for diabetes and medication use while accounting for potential confounders and competing risks.
  
  
  RESULTS
  Among 4,216 women, 13 % developed SBCE during a median follow-up of 6.3 years. 610 women had diabetes of which 76 % used oral diabetes medication and/or insulin. Findings suggested that diabetes increased the risk of recurrence (HR = 1.57; 95 % CI 1.09-2.25) but not overall SBCE (HR = 1.29; 95 % CI 0.94-1.76) or second primary BC (HR = 0.74; 95 % CI 0.39-1.41). Among women with diabetes, insulin use was associated with increased risks of recurrence (HR = 1.94; 95 % CI 1.08-3.48) and all-cause mortality (HR = 2.33; 95 % CI 1.70-3.20). Metformin use was associated with lower all-cause mortality (HR = 0.55; 95 % CI 0.38-0.79).
  
  
  CONCLUSIONS
  Our findings show an association between diabetes and increased recurrence risk, and risk may be greater among insulin users. Metformin may reduce all-cause mortality among BC survivors. Given the growing breast cancer survivor population, further research in larger, more diverse populations is warranted.
authors.affiliation: Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, 833 South Wood Street M/C 871, Chicago, IL, 60612, USA, gcalip@uic.edu.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Calip
authors.forename: Onchee
authors.initials: O
authors.lastname: Yu
authors.forename: Kent F
authors.initials: KF
authors.lastname: Hoskins
authors.forename: Denise M
authors.initials: DM
authors.lastname: Boudreau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000401:mortality; D016016:Proportional Hazards Models; D012306:Risk; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin