Breast cancer survival and mortality among women with type 2 diabetes: a retrospective cohort study

Type 2 diabetes (T2DM) is estimated to affect over 200 million women globally and over 2 million women are estimated to be diagnosed with breast cancer each year. This study aimed to determine the association between breast cancer molecular subtypes and survival in a cohort of women with T2DM. A retrospective cohort study was conducted using linked Scottish population-based data for 3,042 women diagnosed with T2DM prior to their diagnosis of invasive breast cancer between 2010 and 2019 that had complete data available. The women in the cohort were aged 50 to 84 years at the time of breast cancer diagnosis. Univariate analyses were performed using non-parametric ten-year Kaplan Meier (KM) estimates for breast cancer survival by molecular subtype. Hazard ratios (HR) for breast cancer mortality within three years were estimated using Cox proportional hazard models, adjusting for age at breast cancer diagnosis, year of diagnosis, Scottish region, mode of detection, treatment, area-based socioeconomic status, and T2DM duration were conducted. Multiple imputation was performed as a sensitivity analysis. The distribution of molecular subtype based on St Gallen's criteria was luminal A (58%), luminal B (HER2-) (19.2%), triple negative (9.9%), luminal B (HER2 +) (8.5%), and HER2-enriched (4.4%). There were 286 breast cancer deaths in total within three years. KM estimates showed women with HER2-enriched tumours had the worst survival at ages 50 to 69, while those with triple-negative tumours had the worst survival at ages 70 to 84. Adjusted HRs (95% confidence intervals) for mortality over 3 years compared to luminal A were 2.04 (1.43, 2.90) for luminal B (HER2-), 5.68 (3.40, 9.50) for triple negative, 2.22 (1.46, 3.38) for luminal B (HER2 +), and 2.93 (1.63, 5.27) for HER2-enriched. The imputed cohort adjusted HRs were attenuated, particularly for HER2-enriched (HR = 1.71 (1.01, 2.89)) and triple negative (HR = 2.74 (1.72, 4.37)). Like the general population, triple negative and HER2-enriched tumors had worse prognosis compared to luminal A tumors and their association with breast cancer mortality are similar in women with type 2 diabetes and the general population. However, our findings revealed differences in the survival ranking of HER2-enriched and triple-negative subtypes for breast cancer diagnosed in the 50-69 age group between women with type 2 diabetes and the general population, warranting further exploration.