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

摘要 BMI正常的女性通常被认为是健康的，不建议改变生活方式。但新 我们小组进行的研究表明，BMI正常但体重超标的绝经后妇女， 肥胖症患者患雌激素受体阳性乳腺癌的风险大约增加一倍。 这种增加的风险可以通过乳房的局部变化来解释，例如，芳香化酶水平升高， 雌激素生物合成的限速酶，和全身异常，即，水平变化 代谢炎症因子拟议的研究将提供有关可行性和有效性的初步数据 改善身体组成的干预（即，减少肥胖）的绝经后妇女， 体重正常（BMI 18.5 - 24.9），但体脂肪高。如果≥40%的女性受试者 筛选合格，75%的参与者坚持健康指导和个人培训 并且≥80%的受试者完成最终研究评估。招聘工作将在 MD安德森癌症中心的员工。根据绝经状态合格的女性， 自我报告的身高和体重，以及健康和活动变量将与测量的身高和 MD安德森行为研究和治疗中心的体重和全身DXA。62个合格 妇女将被确定并随机分配到16周的饮食（适度的卡路里限制，高强度 每周两次的循环训练，每周150分钟的中等强度有氧运动）或等待列表控制。 我们将评估干预对（1）炎症和代谢功能障碍的循环标志物的影响 与过度肥胖和乳腺癌有关（hsCRP、空腹胰岛素、瘦素、IL-6、甘油三酯、性别 激素结合球蛋白[SHBG]和HDL-胆固醇）;（2）身体组成（%体脂，躯干脂肪质量，脂肪 体重、瘦体重、无脂体重）。探索性结果包括体能（VO 2峰值，坐立测试），行为 （体力活动、能量摄入、宏量营养素消耗）和生活质量（全球健康相关质量） 生活，身体功能，睡眠，更年期症状）。该项目的预期成果是 证明生活方式干预的可行性，将用于更大规模的试验，以评估 身体成分的变化对乳腺癌风险的生物标志物。生物标志物和身体成分数据 R21产生的结果将用于估计效应量和结果方差， 大型随机对照试验。拟议中的项目和未来的试验将推动癌症领域的发展 预防和控制，为降低有乳腺癌风险因素的妇女患乳腺癌的风险提供有用的工具， 帮助他们做出明智的生活方式选择，以降低癌症风险。

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.