Reducing breast cancer risk through modifying body composition and decreasing inflammation in normal weight women

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ABSTRACT Women of normal BMI are typically seen as healthy and not advised to make lifestyle changes. However, new research conducted by our group shows that postmenopausal women who have normal BMI but excess adiposity have approximately a doubling in the risk of developing estrogen receptor-positive breast cancer. This increased risk may be explained by both local changes in the breast, e.g., elevated levels of aromatase, the rate-limiting enzyme for estrogen biosynthesis, and systemic abnormalities, i.e., changes in levels of metabo-inflammatory factors. The proposed study will provide preliminary data on the feasibility and efficacy of an intervention to improve body composition (i.e., reduce adiposity) in postmenopausal women who have a normal weight (BMI 18.5 – 24.9) but high body fat. The study will be considered feasible if ≥40% of the women screened are eligible, 75% of the participants are adherent to the health coaching and personal training sessions, and ≥80% of participants complete the final study assessment. Recruitment will be done in the employee population at MD Anderson Cancer Center. Women who are eligible based on menopausal status, self-reported height and weight, and health and activity variables will be screened with measured height and weight and whole-body DXA in MD Anderson’s Behavioral Research and Treatment Center. Sixty-two eligible women will be identified and randomized to either the 16-week diet (modest calorie restriction, high intensity circuit training twice a week, 150 minutes of moderate intensity aerobic exercise per week) or a wait list control. We will assess effects of intervention on (1) circulating markers of inflammation and metabolic dysfunction linked to both excess adiposity and breast cancer (hsCRP, fasting insulin, leptin, IL-6, triglycerides, sex hormone binding globulin [SHBG] and HDL-cholesterol); (2) body composition (% body fat, trunk fat mass, fat mass, lean mass, fat-free mass). Exploratory outcomes include fitness (VO2peak, sit-to-stand test), behavior (physical activity, energy intake, macronutrient consumption), and quality of life (global health-related quality of life, physical functioning, sleep, menopausal symptoms).The expected outcome of this project is the demonstration of feasibility of the lifestyle intervention that will be used for a larger trial to assess the impact of changes in body composition on biomarkers of breast cancer risk. The biomarker and body composition data produced by this R21 will be used to estimate effect sizes and variance of outcomes that will be used to plan a larger randomized controlled trial. The proposed project and future trial will advance the field in cancer prevention and control by providing a useful tool for breast cancer risk reduction in women with this risk factor, helping them make informed lifestyle choices to reduce their cancer risk.