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

通过改变正常体重女性的身体成分和减少炎症来降低乳腺癌风险

• 批准号: 9896407
• 负责人: KAREN M BASEN-ENGQUIST
• 金额: $ 19.97万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-14 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896407
• 关键词: Aerobic; Aerobic Exercise; Anabolism; Aromatase; Behavior; Behavior Therapy; Behavioral Research; Biological Markers; Body Composition; Body fat; Body mass index; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; C-reactive protein; Caloric Restriction; Cancer Center; Cancer Control; Consumption; Data; Diet; Dietary Intervention; Dual-Energy X-Ray Absorptiometry; Employee; Energy Intake; Enzymes; Estrogen receptor positive; Estrogens; Fasting; Fatty acid glycerol esters; Funding; Future; Goals; Health; Health Personnel; Height; High Density Lipoprotein Cholesterol; Inflammation; Inflammatory; Insulin; Interleukin-6; Intervention; Intervention Trial; Leptin; Life Style; Link; Macronutrients Nutrition; Measures; Menopausal Status; Menopausal Symptom; Metabolic; Metabolic dysfunction; Muscular Atrophy; Normal Range; Obesity; Outcome; Participant; Patient Self-Report; Physical Function; Physical activity; Population; Population Intervention; Postmenopause; Prevention program; Prevention strategy; Primary Prevention; Proteins; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Research; Risk; Risk Factors; Risk Reduction; Sex Hormone-Binding Globulin; Sleep; Testing; Thinness; Training; Treatment Efficacy; Triglycerides; United States National Institutes of Health; Waiting Lists; Weight; Woman; Women' s Health; adiponectin; base; cancer prevention; cancer risk; circulating biomarkers; diet and exercise; exercise intervention; fitness; global health; health related quality of life; high risk; improved; inflammatory marker; intervention effect; lifestyle intervention; malignant breast neoplasm; muscle form; recruit; tool; treatment center

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.

抽象的 普通BMI的妇女通常被视为健康，并且不建议改变生活方式。但是，新的 我们小组进行的研究表明，绝经后妇女的BMI正常但超过 肥胖的风险大约增加了雌激素受体阳性乳腺癌的风险。 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， 雌激素生物合成和全身异常的限速酶，即 代谢炎症因素。拟议的研究将提供有关可行性和效率的初步数据 一种干预措施，以改善具有一个具有 正常重量（BMI 18.5 - 24.9），但体内脂肪高。如果≥40％的女性，该研究将被认为是可行的 筛选有资格，有75％的参与者遵守健康教练和个人培训 会议，≥80％的参与者完成了最终研究评估。招聘将在 MD安德森癌症中心的员工人口。根据绝经状态符合条件的妇女， 自我报告的身高和体重，健康和活动变量将以测量的身高和 MD Anderson的行为研究和治疗中心中的体重和全身DXA。六十二个符合条件 妇女将被识别并随机分为16周饮食（适度的卡路里限制，高强度 每周两次电路训练，每周进行150分钟的中等强度有氧运动）或等待名单控制。 我们将评估干预对（1）炎症和代谢功能障碍的循环标记的影响 与过量肥胖和乳腺癌有关（HSCRP，禁食胰岛素，瘦素，IL-6，甘油三酸酯，性别 同种结合球蛋白[SHBG]和HDL-胆固醇）； （2）身体成分（％体内脂肪，树干脂肪量，脂肪 质量，瘦质量，无脂肪质量）。探索性结果包括健身（VO2PEAK，坐下测试），行为 （体育锻炼，能量摄入，大量营养素消费）和生活质量（全球与健康相关的质量 生活，身体功能，睡眠，更年期症状）。该项目的预期结果是 演示生活方式干预的可行性，将用于更大的试验来评估 乳腺癌风险生物标志物的身体成分变化。生物标志物和身体组成数据 该R21产生的将用于估计效应大小和结果的差异，这些结果将用于计划A 较大的随机对照试验。拟议的项目和未来的试验将推进癌症领域 通过为患有这种危险因素的女性降低乳腺癌风险降低乳腺癌风险的有用工具，预防和控制 帮助他们做出明智的生活方式选择，以降低癌症的风险。