Comparative Effect of Initiating Metformin Versus Sulfonylureas on Breast Cancer Risk in Older Women.
Several observational studies have reported that metformin may be associated with reduced risk of breast cancer; however, many of these studies were affected by time-related biases such as immortal time bias and time-window bias. This study aimed to examine the relative risk of breast cancer for older women initiating metformin versus sulfonylureas while avoiding such biases.



The study cohort consisted of women aged 65+ who initiated monotherapy with metformin (n = 45,900) or sulfonylureas (n = 13,904) and were free of cancer and renal disease within 6 months before treatment initiation using 2007-2012 US Medicare claims data. We followed treatment initiators for incident breast cancer, and estimated hazard ratios using weighted Cox models. Unmeasured confounding by body mass index and smoking was further adjusted by propensity score calibration using external information from Medicare Current Beneficiary Survey 2006-2009 panels.



During 58,835 and 16,366 person-years of follow-up, 385 initiators of metformin treatment and 95 of sulfonylurea were diagnosed with breast cancer. Metformin initiators did not have a reduced risk of breast cancer compared with sulfonylurea initiators (hazard ratio: 1.2; 95% confidence interval: 0.94, 1.6). Externally controlling for body mass index and smoking did not affect the estimates.



The findings of this study provide no support for a reduced risk of breast cancer after initiation of metformin compared with a clinical alternative in older women. This study is limited by the relatively short follow-up time and we cannot exclude the possible benefits of long-time metformin use on breast cancer risk.
aDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; bDepartment of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; and cDepartment of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Jin-Liern
JL
Hong
Michele
M
Jonsson Funk
John B
JB
Buse
Louise M
LM
Henderson
Jennifer L
JL
Lund
Virginia
V
Pate
Til
T
Stürmer
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008687:Metformin / Q000627:therapeutic use*; D057216:Propensity Score; D016016:Proportional Hazards Models; D065840:Protective Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin