Abstract
Breast cancer and type 2 diabetes mellitus (T2DM) are prevalent global health concerns, often sharing overlapping pathophysiological mechanisms. This study aimed to characterize the association of type 2 diabetes mellitus (T2DM) with the histopathological features of non-metastatic breast cancer in Chinese women and evaluate whether glycemic control, diabetes duration, and treatment were involved. A retrospective cross-sectional analysis was conducted on 924 patients with stage I-III ductal breast cancer, equally divided into diabetic (n = 462) and nondiabetic (n = 462) groups. Patients were stratified by fasting blood glucose (FBG) levels, use of metformin and insulin, and diabetes duration. The expression of hormone receptors estrogen and progesterone (ER, PR), human epidermal growth factor receptor 2 (HER2), Ki-67, histological grade, lymph node metastasis, and pathological tumor node metastasis (pTNM) staging were analyzed. Diabetic patients exhibited a higher incidence of triple-negative breast cancer (TNBC) and a lower incidence of HER2-positive breast cancer compared to nondiabetic patients. Poor glycemic control (FBG ≥ 10 mmol/L) was associated with a higher risk of TNBC, histological grade III disease, and lower ER-positive rates compared to those with FBG < 6.1 mmol/L. Patients taking metformin had an increased likelihood of TNBC and decreased ER-positive rates. Insulin-treated patients demonstrated a lower prevalence of pTNM stage I cancers but a nearly fivefold increase in ductal carcinoma in situ (DCIS). Those receiving combination treatment of metformin and insulin were also more likely to present with DCIS. Patients with a longer diabetes duration (≥ 7 years) had significantly lower risks of TNBC and HER2-positive breast cancer but were more likely to have ER- and PR-positive subtypes and histological grade I tumors. These findings highlight the impact of T2DM, glycemic control, and diabetes management on the molecular and histopathological features of non-metastatic breast cancer. While associations were identified, causality could not be determined due to the cross-sectional design. Understanding these associations could guide tailored treatment strategies for diabetic breast cancer patients.