title: Time-Varying Risk for Breast Cancer Following Initiation of Glucose-Lowering Therapy in Women with Type 2 Diabetes: Exploring Detection Bias.
abstract: OBJECTIVE
  To explore detection bias in the association between glucose-lowering therapies and breast cancer in a cohort of women with type 2 diabetes.
  
  
  METHODS
  This was a retrospective, population-based cohort study. We identified new users of metformin, sulfonylureas, thiazolidinediones and insulin during the index period of January 1, 2003, to December 31, 2010. The main outcome was incident breast cancer, and patients were followed up from drug exposure index date until death, diagnosis of another type of cancer, termination of medical insurance or December 31, 2010. To explore detection bias, we split follow-up time into 2 discrete time periods of 0 to 3 months and 3 months to 6 years after drug index date. We performed time-varying Cox regression analyses, including duration of cumulative drug exposure and ever/never drug exposure for each glucose-lowering therapy into our model. The reference was no use of the same drug-exposure category.
  
  
  RESULTS
  There were 22,169 women with type 2 diabetes, with a mean (SD) age of 53.0 (9.2) years and mean (SD) follow up of 2.2 (1.5) years. Hazard ratios for breast cancer in the first 3 months following initiation of metformin, sulfonylurea or thiazolidinedione were 0.66 (0.43 to 1.02), 0.74 (0.44 to 1.25) and 0.67 (0.38 to 1.18), respectively. In the later period of 3 months to 6 years following drug start, hazard ratios (95% CI) for breast cancer were 1.00 (0.98 to 1.02), 1.01 (0.98 to 1.03) and 0.98 (0.95 to 1.01) for metformin, sulfonylurea and thiazolidinedione cumulative exposure, respectively.
  
  
  CONCLUSIONS
  Our findings suggest that no detection bias exists for glucose-lowering therapies and breast cancer in this population.
authors.affiliation: Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Bowker
authors.affiliation: Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mu
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Dean T
authors.initials: DT
authors.lastname: Eurich
authors.affiliation: Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada. Electronic address: jeff.johnson@ualberta.ca.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin
keywords: breast cancer; cancer du sein; cohort study; diabète de type 2; epidemiology; glucose-lowering therapies; traitements hypoglycémiants; type 2 diabetes; épidémiologie; étude de cohorte