| アブストラクト | OBJECTIVE: Numerous observational studies have reported significant reductions in cancer outcomes, including breast cancer in women, with metformin use. However, most studies were affected by immortal time bias. We assessed whether metformin use in women diagnosed with breast cancer is associated with lower breast cancer-related and all-cause mortality and illustrate the impact of immortal time bias on the results. STUDY DESIGN AND SETTING: The Clinical Practice Research Datalink (CPRD) was used to identify a base cohort of all women with a new diagnosis of breast cancer and type 2 diabetes, at least 18 years of age, between 1998 and 2020. We employed the prevalent new-user design to match metformin initiators 1:1 with non-users on a prior diabetes diagnosis and time-conditional propensity scores. We also used the naive approach that introduces immortal time in classifying metformin users. Hazard ratios (HR) and 95% confidence intervals (CI) of all-cause and breast cancer-related death were estimated. RESULTS: The base cohort included 13,314 women newly diagnosed with breast cancer and with type 2 diabetes, before (n=4,761) and after (n=8,553) their breast cancer diagnosis, of which 5,047 initiated metformin during follow-up. The prevalent new-user design included 4,923 metformin initiators and 4,923 matched non-users. The HRs of breast cancer-related and all-cause mortality were 1.12 (95% CI: 0.98-1.28) and 0.96 (95% CI: 0.89-1.05), respectively. The naive approach, among women with diabetes at cohort entry, which included 1,354 metformin users and 3,407 metformin non-users, resulted in adjusted HRs of 0.45 (95% CI: 0.40-0.50) and 0.58 (95% CI: 0.54-0.62) for breast cancer and all-cause mortality. CONCLUSIONS: In this study, the use of metformin was not associated with a reduced risk of breast cancer-related and all-cause mortality. Using the flawed approach not accounting for immortal time bias, we confirmed the implausible beneficial effects of metformin on breast cancer and all-cause mortality reported in previous studies. |
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| ジャーナル名 | Journal of clinical epidemiology |
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| Pubmed追加日 | 2025/6/28 |
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| 投稿者 | Khouri, Charles; Dell'Aniello, Sophie; Yin, Hui; Azoulay, Laurent; Suissa, Samy |
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| 組織名 | Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital,;Montreal, Canada; Univ. Grenoble Alpes, Pharmacovigilance unit, Grenoble Alpes;University Hospital, Grenoble, France; Univ. Grenoble Alpes, HP2 laboratory,;INSERM U 1300, Grenoble, France.;Montreal, Canada.;Montreal, Canada; Departments of Epidemiology, Biostatistics and Occupational;Health, and Medicine, McGill University, Montreal, Canada; Gerald Bronfman;Department of Oncology, McGill University, Canada.;Health, and Medicine, McGill University, Montreal, Canada. Electronic address:;samy.suissa@mcgill.ca. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/40578405/ |
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