Abstract 724: Examining the effects of obesity and weight loss on mammary tumor inflammation and fibrosis

Abstract

Abstract Obesity significantly increases risk of breast cancer development, and following diagnosis, obese breast cancer patients have an overall worsened prognosis. The complex relationship of obesity to breast cancer growth and aggressiveness must continue to be examined. Within breast adipose tissue, obesity causes a state of chronic, macrophage-driven inflammation. Chronic inflammation is associated with increased extracellular matrix (ECM) deposition. Increased collagen within the mammary microenvironment is a risk factor for tumor formation, as well as more aggressive tumors, in mouse models. In breast tumors from obese patients, tumor desmoplasia is also found to be increased. To better understand how obesity affects mammary tumor growth, inflammation, and fibrosis, we used a diet-induced obesity mouse model paired with the estrogen receptor alpha (ERα)+ TC2 mammary tumor cell line in female FVB mice. We observed that TC2 mammary tumors grew significantly faster in obese mice compared to lean mice and had significantly more macrophage infiltration. TC2 tumors from obese mice also had significantly more collagen deposition than TC2 tumors from lean mice, indicating that obesity leads to more fibrotic tumors. To identify how weight loss alters the mammary gland and mammary tumor microenvironments, obese mice were switched from a high-fat diet to a low-fat diet for six weeks, to induce weight loss. In non-tumor-bearing mammary glands, weight loss led to a significantly decreased number of crown-like structures, a marker of adipose tissue inflammation, similar to observations in human adipose tissue. TC2 mammary tumors grew at an intermediate rate between tumors from lean and obese mice, indicating that weight loss may be a viable option to reduce tumor aggressiveness, particularly for obese patients with other breast cancer risk factors. Understanding these weight-related changes in the mammary gland and mammary tumor microenvironments will provide greater insight into possible interventions for obese breast cancer patients. Citation Format: Genevra M. Kuziel, Lisa M. Arendt. Examining the effects of obesity and weight loss on mammary tumor inflammation and fibrosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 724.