Abstract P065: Effects of metformin on breast tissue inflammation in premenopausal women with components of metabolic syndrome

Background: Obesity, with increasing worldwide prevalence, is associated with increased breast cancer burden. The association is attributed to multiple metabolic disturbances including chronic inflammation due to dysfunctional adipose tissue. Features of local breast adipose tissue inflammation such as macrophage infiltration and an enriched pro-inflammatory gene signature were recently reported in mouse models of obesity and in women with high adiposity or metabolic disorders. Strategies that can reduce obesity-induced chronic inflammation may lead to reduction of breast cancer risk. Metformin, a widely used anti-diabetic drug, exerts favorable effects on multiple metabolic disturbances. This study aims to evaluate the clinical effects of metformin on breast tissue inflammation. Methods: Macrophage infiltration and polarization were determined in breast core needle biopsies collected at baseline and 6 months after agent intervention from a Phase II randomized, double-blind, placebo-controlled trial of metformin in premenopausal women with components of metabolic syndrome. Macrophage infiltration was assessed using a pan macrophage marker (CD68) by immunohistochemistry (IHC). M1 and M2 macrophages were assessed using CD40 and CD206 surface markers, respectively, by IHC. The primary endpoint is the change in macrophage density in breast adipose tissue. Secondary endpoints include the change in macrophage density in breast stroma and epithelium tissues, the proportion of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages in breast adipose, stroma, and epithelium tissues. Results: Baseline biopsies from 76 participants (40 in the metformin arm and 36 in the placebo arm) were available for CD68 analysis. The baseline CD68 density was 22.48 ± 3.25, 67.26 ± 9.68, 418.81± 71.02 (mean±SE) per mm2 in breast adipose, stroma, and epithelium tissues, respectively. Biopsies from 71 participants (34 in the metformin arm and 37 in the placebo arm) were available for CD68 analysis at 6 months. Comparing to placebo, metformin intervention led to a significant reduction in CD68 density in breast adipose tissue (p = 0.01) but did not change the CD68 density in breast epithelium and stroma tissues. Conclusion: Metformin intervention resulted in favorable changes in macrophage infiltration in breast adipose tissue in premenopausal women with component of metabolic syndrome. Studies are ongoing to evaluate the effects of metformin on macrophage polarization. Citation Format: Liane E. Pinto, Sara Centuori, Jose Guillen-Rodriguez, Denise J. Roe, Edgar Tapia, Pavani Chalasani, H-H. Sherry Chow. Effects of metformin on breast tissue inflammation in premenopausal women with components of metabolic syndrome. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P065.