Abstract 5902: Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses’ Health Studies

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Abstract Background: Type 2 diabetes (T2D) has been associated with increased risk of breast cancer. However, the role of metformin, the first-line anti-diabetic drug, in breast cancer carcinogenesis has not been elucidated completely. We aimed to examine further the association between the use of metformin and other anti-diabetic medication and breast cancer incidence within two large prospective cohort studies. Methods: We followed 184,437 women who participated in the Nurses’ Health Study (NHS;1994-2016) and the NHSII (1995-2017), with the baseline tied to the date metformin was introduced into the United States market. Information on T2D diagnosis, metformin, and other anti-diabetic medication, and other covariates were self-reported at baseline and repeatedly assessed by follow-up questionnaires every two to four years. Breast cancer cases were self-reported and confirmed by medical record review. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between metformin/other anti-diabetic medication use and breast cancer incidence were estimated using Cox proportional hazards regression models. Results: During 3,412,366 person-years of follow-up, we ascertained 9,442 incident invasive breast cancer cases, of which 720 were among women with T2D. Compared with women without T2D (n=168,498), similar risks of developing breast cancer were observed among those who ever used metformin (HR =0.95; 95%CI=0.79-1.13) and among those who received medications other than metformin (HR =1.11; 95%CI=0.91-1.37). Among women with T2D (n=15,939), compared with never metformin users, ever use of metformin overall was not associated with breast cancer (HR =0.90; 95%CI=0.72-1.13), but a lower risk of breast cancer was observed among past metformin users (HR =0.72; 95%CI=0.52-0.99). Longer duration of metformin use was not associated with risk of breast cancer (each 2-year interval: HR =0.98; 95%CI=0.93-1.03, p-trend=0.32). However, among women with substantial weight increase since age 18 (>25 kg), greater than 5 years of metformin use was associated with a lower risk of breast cancer (HR =0.62; 95%CI=0.43-0.89). Conclusion: Although we observed inverse associations among past metformin users, similar associations were not found among current users. Overall, metformin use was not strongly associated with the risk of developing breast cancer among the general cohort population or among women with T2D. Citation Format: Tengteng Wang, Jae H. Kang, Boyang Chai, Wendy Y. Chen, Michelle D. Holmes, Jennifer Erdrich, Edward L. Giovannucci, Frank B. Hu, Bernard A. Rosner, Rulla M. Tamimi, Walter C. Willett, A. Heather Eliassen. Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses’ Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5902.