Poster #14 - Aditya Shah

Tumor subtype and clinical factors mediate the impact of tumor PPARɣ expression on outcomes in patients with primary breast cancer.

Aditya Shah1,2, Katie Liu1,3, Ryan Liu1, 4, Gautham Ramshankar1, Curtis J. Perry MD, Ph.D.5,6, and Rachel J. Perry Ph.D1* 1Departments of Cellular & Molecular Physiology, Internal Medicine (Endocrinology), and Comparative Medicine, Yale University, New Haven, CT, United States 2Woodbridge Academy Magnet School, Woodbridge, NJ, United States 3Cedar Park High School, Cedar Park, TX, United States 4Brown University, Providence, RI, United States 5Yale Cancer Center, New Haven, CT, United States 6Department of Internal Medicine (Hematology/Oncology), Yale University, New Haven, CT, United States

Breast cancer progression is influenced by tumor subtype, metabolic environment, and patient factors, including menopausal status and BMI. In this study, we use publicly available data to investigate the prognostic relevance of PPARɣ gene expression, a key regulator of lipid metabolism, and its implications across different subgroups and study proliferation of adipose tissue in patients of different tumor types and phenotypic cohorts. We analyzed RNA-seq data from 1094 primary breast cancer patients in the TCGA-BRCA cohort, stratifying patients by PPARɣ expression, menopausal status, and tumor receptor subtype (ER+, HER2-, TNBC) using the UCSC Xena Browser Viewer. Kaplan-Meier analysis revealed that high PPARɣ expression (≥ 6.903 FPKM) was significantly associated with both improved overall and disease-specific survival, particularly in premenopausal patients. Complementing this, we analyzed publicly available PET-CT scans from 69 breast cancer patients in the ACRIN-6888 clinical trial from the The Cancer Imaging Archive (TCIA), focusing on SUV metrics (mean, max, peak) of a cell cycle tracer, 3'-deoxy-3'-[¹⁸F]fluorothymidine (18F-FLT) in visceral and combined (subcutaneous and visceral) adipose tissue at the L3/L4 level. Postmenopausal patients had lower visceral SUVmean (0.705 vs 0.776), and patients with ER+ tumors or non-TNBC tumors showed significantly lower SUVpeak and SUVmax of adipose tissue compared to their counterparts (p < 0.05), indicating metabolic/proliferative reprogramming of adipose tissue based on tumor type. Our study shapes a deeper understanding of PPARɣ as a therapeutic target in breast cancer via lipid metabolism pathways; the changes in adipose tissue proliferation across different cohorts show the strong potential for subtype-specific breast cancer treatment.