WISER Sister

聪明的姐姐

• 批准号: 8269112
• 负责人: Kathryn H. Schmitz
• 金额: $ 61.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269112
• 关键词: Address; Adherence; Adverse effects; Affect; Age; Am 80; Area Under Curve; BRCA1 gene; Body Composition; Body Size; Body Weight; Body fat; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; Characteristics; Control Groups; Data; Development; Diet; Dose; Educational Intervention; Estradiol; Estriol; Estrogen Metabolism; Estrogens; Estrone; Exercise; Family; Fatty acid glycerol esters; Genetic; Glucuronides; Goals; Gonadal Steroid Hormones; Guidelines; Health Benefit; Health Promotion; Heart Rate; High Risk Woman; Home environment; Hormonal; Hormones; Image; Intervention; Length; Leptin; Luteal Phase; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Menstrual cycle; Minnesota; Mitogens; Mitotic Activity; Monitor; Mutation; Operative Surgical Procedures; Outcome; Outcome Measure; Participant; Pennsylvania; Pharmaceutical Preparations; Physiological; Pregnanediol; Premenopause; Prevention; Preventive; Progesterone; Prolactin; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Recording of previous events; Recruitment Activity; Research Personnel; Risk; Risk Factors; Sampling; Screening procedure; Serum; Sister; Spottings; T-Cell Receptor-Rearrangement Excision DNA Circles; Testing; Testosterone; Tissues; Training; Universities; Urine; Visit; Waiting Lists; Weight maintenance regimen; Woman; Women' s Group; Work; adipokines; adiponectin; aged; base; breast density; cancer risk; cohort; energy balance; fitness; group intervention; improved; innovation; lifetime risk; malignant breast neoplasm; neoplastic; non-genetic; novel; older women; primary outcome; proliferative phase Menstrual cycle; public health relevance; response; steroid hormone; success; trait; tumor; urinary; young woman

DESCRIPTION (provided by investigator): A subset of premenopausal women is at significantly elevated risk for breast cancer due to specific genetic traits (e.g. BRCA1 or 2 mutations) and or strong family history. Effective breast cancer prevention available for high-risk women (drugs or surgery) are hormonal interventions; the strongest basis for breast cancer prevention among high risk women is through hormonal intervention. However, both surgical and drug based prevention have serious negative long term consequences that may not be acceptable to many women. We propose a preventive exercise intervention for increased risk women that might address the same hormonal issues, yet have fewer serious side effects and not impact negatively on quality of life. Exercise training also has many well established positive health benefits beyond those hypothesized herein. These women are highly motivated to reduce their risk. Therefore, even if the alteration in risk is marginal (e.g. consistent with smaller tumor size, delayed onset of breast cancer, or reduced breast density that would improve the success of early screening), women at increased risk deserve to know what they can reasonably expect from regular exercise with regard to reducing breast cancer risk. The overarching goal of the proposed dose response trial is to establish the effects of 5 months of low or high dose exercise on variables known to be associated with breast mitotic activity, among a cohort of 160 women with a > 18 percent lifetime risk for breast cancer. The exercise doses were chosen to approximate the current public health guidelines for health promotion (150 minutes weekly) and weight control (300 minutes weekly). The primary hypothesis to be tested is that exercise training will result in a significant decrease of estrogen exposure, and in a dose response manner. The measurement of estrogen exposure is a particular innovation of the proposed work compared to prior studies that have examined the effects of exercise on estrogens. Daily spot urinary samples will be collected over 2 menstrual cycles before and after the exercise training intervention and the primary outcome will be total hormone exposure as assessed by estrogen area under the curve. Study measures include known mitogens (e.g. daily urinary estrogen and progesterone over multiple menstrual cycles; estrogen metabolites; other sex steroid hormones), as well as fibroglandular tissue volume from MRI scans (as a surrogate of breast mitotic activity). Changes in body composition and adipokines will also be assessed. In combination with data from an ongoing parallel trial in low risk women (the WISER study), the proposed work will provide novel information regarding differences, or lack thereof, in levels of commonly accepted risk factors for breast cancer (estrogens, estrogen metabolism, other sex steroid hormones, adipokines, and body composition), as well as comparisons of the effects of exercise training on these outcomes. PUBLIC HEALTH RELEVANCE: WISER Sister is a randomized controlled trial that will add significantly to understanding the potential for five months of exercise training to reduce breast cancer risk factors (including estrogens and MRI breast imaging) in 160 young women (aged 18-35) with significantly increased risk. In combination with data from an ongoing parallel trial in low risk women (the WISER study), the proposed work will provide novel information regarding differences, or lack thereof, in levels of commonly accepted risk factors for breast cancer (estrogens, breast density from MRI, estrogen metabolism, other steroid hormones, adipokines, and body composition), as well as comparisons of the effects of exercise training on these outcomes. The WISER Sister study will randomize 160 young women with elevated breast cancer risk into 3 equal sized groups: wait list control, low dose exercise (150 minutes weekly, to approximate the current public health recommendations for exercise for general health promotion), and high dose exercise (building to 300 minutes weekly, to approximate the public health recommendations for weight control).

描述（由研究者提供）：由于特定的遗传特征（例如BRCA1或2突变）和 /或 /或 /或 /或 /或强大的家族史，因此，绝经前妇女的一部分乳腺癌风险显着升高。可用于高危妇女（药物或手术）的有效预防乳腺癌是荷尔蒙干预措施；高风险女性预防乳腺癌的最强基础是荷尔蒙干预。但是，手术和基于药物的预防都有严重的长期负面后果，许多妇女可能无法接受。我们建议对增加的风险女性进行预防性锻炼干预，以解决相同的荷尔蒙问题，但严重副作用较少，不会对生活质量产生负面影响。锻炼训练还具有许多良好的积极健康益处，超出了本文假设的益处。这些妇女有力地降低自己的风险。因此，即使风险的改变是边缘的（例如，与较小的肿瘤大小，乳腺癌的延迟开始或乳腺癌密度降低相一致，从而改善早期筛查的成功），风险增加的妇女也应该知道自己在降低乳腺癌风险方面可以合理地期望进行定期运动。拟议的剂量反应试验的总体目标是建立5个月低剂量运动对已知与乳腺丝分裂活性相关的变量的影响，这是160名妇女的乳腺癌风险约18％的女性。选择运动剂量以近似目前的健康促进公共卫生指南（每周150分钟）和体重控制（每周300分钟）。要测试的主要假设是，运动训练将导致雌激素暴露和剂量反应方式显着降低。与先前研究了运动对雌激素的影响相比，雌激素暴露的测量是拟议工作的特殊创新。在运动训练干预之前和之后，将在2个月经周期内收集每日尿液样品，而主要结果将是曲线下雌激素面积评估的总激素暴露。研究措施包括已知的有丝分裂原（例如，在多个月经周期中的每日尿中雌激素和孕酮；雌激素代谢产物；其他性类固醇激素），以及MRI扫描（作为乳腺丝分裂活性的替代乳腺剂量）中的纤维球界组织体积。身体成分和脂肪因子的变化也将被评估。结合低风险女性正在进行的平行试验的数据（这项明智的研究），拟议的工作将提供有关乳腺癌常见的危险因素（雌激素，雌激素代谢，其他性类固醇激素，脂肪因子，脂肪因子，脂肪因子和身体成分）的新颖信息，以及对这些锻炼培训的比较。 公共卫生相关性：Wiser Sister是一项随机对照试验，将大大增加160名年轻妇女（18-35岁）的乳腺癌危险因素（包括雌激素和MRI乳房成像）的五个月运动训练的潜力，并具有显着增加的风险。结合来自低风险女性正在进行的平行试验的数据（较明智的研究），拟议的工作将提供有关差异或缺乏差异的新信息，这些信息在乳腺癌（雌激素，MRI，雌激素代谢产生的乳腺密度，雌激素代谢，其他类固醇激素，其他类固醇激素，脂肪因素，脂肪因子和身体组成）的水平以及对比较效果的效果效果效果。明智的姐妹研究将将160名乳腺癌风险升高的年轻女性随机分为3个相等大小的组：等待名单控制，低剂量运动（每周150分钟，以近似于当前的公共健康促进锻炼建议）和高剂量锻炼（每周建立300分钟至300分钟，以近似为体重控制的公共卫生建议）。

项目成果

The dose-response effects of aerobic exercise on musculoskeletal injury: a post hoc analysis of a randomized trial.

• DOI: 10.1080/15438627.2017.1314295
• 发表时间: 2017-07
• 期刊: Research in sports medicine (Print)
• 作者: Brown JC;Schmitz KH
• 通讯作者: Schmitz KH

The Dose-Response Effects of Aerobic Exercise on Body Composition and Breast Tissue among Women at High Risk for Breast Cancer: A Randomized Trial.

• DOI: 10.1158/1940-6207.capr-15-0408
• 发表时间: 2016-07
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Brown JC;Kontos D;Schnall MD;Wu S;Schmitz KH
• 通讯作者: Schmitz KH