The influence of diabetes mellitus on blood vessels amounts and immune status in case of breast cancer

Vol. 66 No. 3, 2025

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Ecaterina Foca, Dumitru Brinza, Ecaterina Carpenco, Valeriu David, Lilian Saptefrati, Veaceslav Fulga

Background: Breast cancer (BC) remains one of the most prevalent malignancies worldwide, and its progression can be influenced by systemic conditions such as type 2 diabetes mellitus (T2DM). Both diseases share common mechanisms of metabolic dysregulation, chronic inflammation, and vascular dysfunction that may reshape the tumor microenvironment (TME). Aim: To conduct a comparative evaluation of the vascular and immune components of the BC microenvironment in patients with and without T2DM, as well as in normal mammary tissue, with particular emphasis on cluster of differentiation (CD)34+ microvessel density (MVD), T-cell subsets (CD3+, CD4+, CD8+), and their association with hormonal receptor status and proliferative index (Ki67). Materials and Methods: Immunohistochemical analysis was performed on 58 invasive ductal carcinomas (29 T2DM-associated, 29 non-diabetic) and 10 normal breast samples. Quantification of immune and vascular markers was correlated with clinical and morphological parameters using Spearman s test and Welch statistics (p<=0.05). Results: T2DM-associated BCs demonstrated significantly increased intratumoral MVD (p=0.03) and decreased intratumoral CD3+, CD4+, and CD8+ lymphocytes compared with non-diabetic tumors, indicating an immune-excluded phenotype. Blood glucose correlated positively with CD34+ vessel content and inversely with Ki67 expression (rs=-0.29, p=0.05). Peritumoral CD8+ cells were positively associated with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status, suggesting hormonal modulation of immune infiltration. Conclusions: T2DM promotes vascular proliferation and suppresses intratumoral immune activity in BC, creating an angiogenic yet immunosuppressed microenvironment. These findings highlight the impact of metabolic imbalance on tumor biology and underscore the need for integrating metabolic control and immunomodulatory strategies in the management of diabetic BC patients.

Corresponding author: Ecaterina Carpenco, Assistant Professor, PhD; e-mail: ecaterina.carpenco@usmf.md

DOI: 10.47162/RJME.66.3.12 Download PDF
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