Affiliation:
1. Department of Epidemiology and Biostatistics University of California, San Francisco San Francisco California USA
2. Department of Breast Surgery National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
3. Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
4. Department of Psychiatry University of California, San Francisco San Francisco California USA
5. UCSF Library University of California, San Francisco San Francisco California USA
6. Department of Urology University of California, San Francisco San Francisco California USA
7. Division of Rheumatology Department of Medicine University of California, San Francisco San Francisco California USA
Abstract
AbstractDiabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta‐analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case‐control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta‐analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11–1.29). The 24 case‐control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13–1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05–1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07–1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85–1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00–1.20), ER‐ (RR = 1.16, 95% CI: 1.04–1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01–1.96). The association estimate for human epidermal growth factor 2‐positive BCa was also positive (RR = 1.21, 95% CI: 0.52–2.82), but the CI was wide and crossed the null. Our meta‐analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.
Funder
Prostate Cancer Foundation
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine