Interactions Among Tumor Subtype, PPARγ 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 utilize publicly available data to investigate the prognostic relevance of PPARγ gene expression, a key regulator of lipid metabolism, and its implications across different subgroups. We also examine the proliferation of adipose tissue in patients with various tumor subtypes and phenotypic cohorts. We analyzed RNA-seq data from 1094 primary breast cancer patients in the TCGA-BRCA cohort, stratifying patients by PPARγ expression, menopausal status, and tumor receptor subtype (ER+, HER2-, TNBC) using the UCSC Xena Browser Viewer. Kaplan-Meier analysis revealed that high PPARγ expression (≥6.903 FPKM) was significantly associated with both improved overall and disease-specific survival, particularly in premenopausal patients. Complementing this, we analyzed PET-CT scans from 69 breast cancer patients in the ACRIN-6888 clinical trial, focusing on SUV metrics (mean, max, peak) of a cell cycle tracer, 3'-deoxy-3'-[¹⁸F]-fluorothymidine (¹⁸F-FLT) in visceral and subcutaneous adipose tissue at the L3/L4 level. Postmenopausal patients had lower visceral SUV_mean (0.705 vs 0.776), and patients with ER+ tumors or non-TNBC tumors showed significantly lower SUV_peak and SUV_max of adipose tissue compared to their counterparts (p < 0.05), indicating metabolic/proliferative reprogramming of adipose tissue based on tumor type. Our study provides a deeper understanding of PPARγ as a therapeutic target in breast cancer through lipid metabolism pathways. The changes in adipose tissue proliferation across cohorts demonstrate the strong potential for subtype-specific breast cancer treatment.