Weight of the Matter: How Metabolic Syndrome Alters the Breast Tumor Microenvironment

• Ishani Vyas, Biological Sciences, University of Delaware

• Leire Arrizabalaga Astigarraga, Cancer Signaling and Microenvironment, Fox Chase Cancer Center
• Aitziber Buqué Martinez, Cancer Signaling and Microenvironment, Fox Chase Cancer Center

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide, with approximately 2.3 million new cases diagnosed each year. Nearly 70% of cases are classified as hormone receptor-positive (HR+). Although advances in therapy have improved survival, 10-40% of patients with HR+ BC experience recurrence. Obesity is a major risk factor for BC and has been associated with a 30-40% higher risk of recurrence in some patient populations, particularly among postmenopausal women. Metabolic syndrome (MetS), a cluster of metabolic abnormalities including obesity, insulin resistance (IR), and type 2 diabetes, affects approximately one in three adults in the United States. These metabolic alterations promote chronic inflammation within white adipose tissue (WAT), leading to changes in immune cell function and cytokine signaling that may contribute to a tumor-supportive microenvironment. However, the mechanisms linking MetS to BC progression remain poorly understood. To investigate how cytokines released by adipocytes influence breast cancer cell behavior, we isolated WAT and immune cells from lean, obese (high-fat diet), and IR (high-fructose diet) mice. The WAT secretome, containing adipocyte-derived cytokines, was collected to condition breast cancer cells culture media either alone or in combination with immune cells. No significant differences in tumor cell proliferation were observed between treatment groups, although trends suggested that adipocyte-derived cytokines from metabolically dysregulated mice may influence tumor cell behavior. These findings support further investigation into how adipocyte-derived cytokines may contribute to the tumor microenvironment and may help explain the relationship between metabolic syndrome and breast cancer progression.