Ouafa Badre, Sue-Ling Chang, Belkacem Abdous, Julie Lemieux, Francine Durocher, André Tchernof, Caroline Diorio
Background/Objectives: Mammary adipose tissue functions as an active endocrine organ, potentially influencing breast carcinogenesis through metabolic and inflammatory mechanisms. This systematic review synthesized evidence on associations between mammary adipocyte size, obesity-related adipose tissue dysfunction, and breast cancer. Methods: A comprehensive literature search was conducted across MEDLINE, EMBASE, CENTRAL, CINAHL and Web of Science (January 2010-September 2025) for observational studies measuring mammary adipocyte size in human breast tissue. Two reviewers independently conducted screening following the Cochrane Review's rigorous methodology, and bias assessment using the ROBINS-E (Risk Of Bias In Non-randomized Studies of Exposure) tool. Random-effects meta-analyses were performed for quantifiable outcomes, with heterogeneity assessed using the I2 statistic. Results: Twenty-one studies were included in the systematic review. Meta-analyses indicated that mammary adipocyte diameter was positively correlated with body mass index (8 studies; n = 720; correlation coefficient (r) = 0.44, 95% CI: 0.29-0.56), crown-like structure (CLS) density (5 studies; n = 383; r = 0.45, 95% confidence interval (CI): 0.36-0.54), aromatase expression (3 studies; n = 333; r = 0.36, 95% CI: 0.05-0.61), and three studies compared adipocyte diameter between CLS-positive and CLS-negative tissue (n = 297; mean difference = 9.69 μm, 95% CI: 4.94-14.44). Conclusions: This review summarizes moderate positive correlations of mammary adipocyte size with systemic adiposity, local breast inflammation, and aromatase expression, supporting a potential role for mammary adipose tissue in obesity-related metabolic dysfunction. Future prospective studies with standardized measurement protocols and improved control for confounding variables are needed to strengthen causal inference and clinical applications.