Abstract SP054: Obesity and Breast Cancer: Body Composition, Metabolic Mediators and Inflammation

Abstract

Abstract Obesity has been associated with an increased risk of postmenopausal breast cancer (predominantly ER+), as well as triple negative premenopausal breast cancer. It has also been associated with an increased risk of breast cancer distant recurrence and death, regardless or menopausal status or IHC defined breast cancer subtype. Obesity effects on recurrence and death are modest, with HRs for either outcome approximating 1.3. Obesity is linked to metabolic alterations that include insulin resistance (with associated high insulin and reduced glucose tolerance), altered lipids and adipokines, hypertension, central obesity, inflammation and increased risks of type 2 diabetes (T2DM) and cardiovascular disease - this constellation of attributes comprises the insulin resistance or metabolic syndrome. There is growing appreciation that BMI [weight (kg)/height (m)2] ≥ 30 kg/m2 is an imperfect measure of both body composition and underlying metabolic status. Recent research has focused on body composition (e.g. central obesity/sarcopenic obesity) and metabolic health (“healthy” obese, “unhealthy” normal weight) as predictors of breast cancer outcomes. Many of the inter-related physiologic changes associated with obesity (including higher levels of insulin, glucose, altered adipokines and, less consistently, circulating inflammatory factors) have individually been associated with increased breast cancer risk and/or poor breast cancer outcomes. These circulating factors, and obesity per se, have, in turn, been associated with changes in breast tissue and tumor micro-environment, including crown-like structures (dying adipocytes surrounded by inflammatory cells) as well as increased infiltration of inflammatory cells, cytokines and chemokines - all of which have been linked to cancer risk and progression in preclinical and/or clinical research. Evidence linking obesity/body composition, circulating obesity-associated physiologic and inflammatory factors to breast cancer outcomes will be discussed as will interventions (notably weight loss, metformin) targeting these factors in breast cancer patients. Recent findings linking breast inflammation to obesity/obesity-associated physiology and breast cancer outcomes will be reviewed. The inter-relatedness of these factors and the likelihood that the breast cancer-obesity link is complex and multifactorial will be highlighted. Citation Format: P Goodwin. Obesity and Breast Cancer: Body Composition, Metabolic Mediators and Inflammation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP054.