Interactions among tumor subtype, <scp>PPARγ</scp> expression, and adipose proliferation shape outcomes in breast cancer

Breast cancer progression is influenced by tumor subtype, metabolic environment, and patient factors, including menopausal status and BMI. In this study, we utilized publicly available data to investigate the prognostic relevance of PPARγ gene's expression across different subgroups. We also examined adipose tissue proliferation in patients with various tumor subtypes and phenotypic cohorts. We analyzed RNA-seq data from primary breast cancer patients in the TCGA-BRCA cohort, stratifying patients by PPARγ expression, menopausal status, and tumor receptor subtype. Kaplan-Meier analyses revealed that high PPARγ expression was associated with improved overall survival, particularly in premenopausal patients. Complementing this, we analyzed PET-CT scans from breast cancer patients in the ACRIN-6888 trial, focusing on standardized uptake value (SUV) metrics of a cell cycle tracer, 3'-deoxy-3'-[18F]-fluorothymidine (¹⁸F-FLT) in visceral and subcutaneous adipose tissue. Postmenopausal patients had lower visceral adipose tissue SUV_mean, and patients with ER+ or non-TNBC tumors showed lower SUV_peak and SUV_max of both adipose tissue types, indicating metabolic/proliferative reprogramming of adipose tissue based on tumor subtype. We hypothesize that PPARγ expression and adipose proliferation differentially affect survival across subtypes and menopausal status, providing deeper insight into PPARγ as a therapeutic target in breast cancer and the potential implications for precision medicine treatments.