Abstract
PURPOSE: Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM. PATIENTS AND METHODS: This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004-2013. The cohort included women diagnosed with T2DM, aged 30-80 years, with no history of breast cancer and with follow-up data for at least 1 year. We used Cox proportional hazards models to estimate the associations of exposures with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Exposures of interest included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glycated hemoglobin A (HbA1c) and systolic blood pressure (SBP). RESULTS: During a median of 4.45 years' follow-up, 183 of 10,183 included women received a breast cancer diagnosis. We observed U-shaped associations with breast cancer incidence for total cholesterol and HDL-C at baseline. Compared with moderate elevations, women had significantly higher breast cancer risks associated with high total cholesterol (aHR, 95% CI: 1.72, 1.15-2.55) and HDL-C (aHR, 95% CI: 1.74, 1.18-2.58) levels, while low total cholesterol (aHR, 95% CI: 1.43, 0.94-2.19) and HDL-C (aHR, 95% CI: 1.44, 0.95-2.17) levels produced marginal effects without significance. Women with high LDL-C levels more often received a breast cancer diagnosis than those with medium levels (aHR, 95% CI: 1.56, 1.03-2.35). CONCLUSION: This real-world dataset highlights the importance of balancing lipid profiles, particularly total cholesterol and HDL-C. Dysregulation of the lipid profile, not the glucose or blood pressure profiles, may increase the risk of breast cancer in women with T2DM.