Metabolic Syndrome and Breast Cancer: Effects of a Combined Exercise Intervention

描述(申请人提供)：K07职业发展奖旨在帮助我实现我的长期目标，即成为一名独立而富有成效的癌症人群运动干预者，能够建立并领导跨学科研究团队，以获得更好的癌症生存结果。我的近期目标是利用这个奖项在与乳腺癌生存相关的领域获得深入的培训，1)提高我在运动生理学方面的技能，以涵盖癌症人群，2)获得关于癌症人群临床试验设计和执行的进一步培训，这是成为一名独立的学术研究员所必需的，3)通过执行这项建议来发展我的独立研究方向，以及4)通过在参加人口科学、医学肿瘤学和霍普市内分泌学系的教育工作坊和研讨会的同时，通过将流行病学研究成果发展成可翻译的干预试验。我提议的培训和研究将使我对流行病学、健康行为、内分泌学、内科肿瘤学和乳腺生理学有一个综合的了解，以更好地发展乳腺癌生存研究方面的专业知识。希望之城国家医疗中心(COHNMC)提供了广泛的资源和职业发展机会，将在该奖项中使用。COHNMC自1918年成立以来，一直处于医学和基础科学研究的前沿。COHNMC提供了一个广阔的环境，有着源远流长的高质量研究历史，其中包括将在我的指导委员会中任职的关键教职员工：Leslie Bernstein博士(主要导师)、Joanne Mortime医学博士(联合导师)和Fuad Kandeel博士(联合导师)。因此，COHNMC的基础部门高度参与了我的职业发展计划，包括人口科学系(Bernstein)、内科肿瘤学和治疗研究部(Mortimer)和糖尿病、内分泌学和新陈代谢系(Kandeel)。每个部门和相关导师将提供独特和灵活的培训机会，这对我的职业发展至关重要，并将为我成为一名独立的癌症研究人员奠定基础。乳腺癌是一种常见病，由于医学和科学的进步，其存活率很高。然而，严重的乳腺癌治疗副作用，如体重增加，在生存期间持续存在，并增加了患新陈代谢相关疾病的风险，包括糖尿病和心血管疾病。这项拟议研究的目标是调查运动干预对绝经前和绝经后乳腺癌幸存者代谢综合征(METS)危险因素的影响。其目的是通过运动干预来减少乳腺癌幸存者体内甲硫氨酸升高的成分，以提高存活率。第一个具体目标是通过测量身体成分、腰围、血压、静息能量消耗(REE)以及血清胰岛素、葡萄糖、血脂和炎症标志物的水平的变化，确定16周的运动干预是否会改善代谢综合征的组成部分。我将100名绝经前和绝经后的乳腺癌幸存者随机分配到对照组或运动组，为期16周。运动干预将包括每周三次监督运动，包括有氧运动和阻力运动。第二个具体目标是通过测量心肺健康和肌肉力量来确定16周的运动干预是否会在癌症相关治疗完成后不久改善乳腺癌幸存者的身体健康。最后，第三个具体目标是通过测量身体成分、腰围、血压和血清胰岛素、葡萄糖、血脂、C反应蛋白、糖化血红蛋白、心肺功能和肌肉力量的变化，来确定乳腺癌幸存者在12周的随访期后是否可以保持运动干预的积极益处。 随着拟议的研究目标的完成，预计在治疗完成后不久进行的为期16周的运动干预将改善1)代谢综合征的组成部分，2)乳腺癌幸存者的身体健康和力量。这些结果将对诊断和治疗后的癌症存活率和疾病风险产生重大影响。乳腺癌的存活率相对较高，这意味着需要健康的生活，以减少患其他疾病的风险，如糖尿病和心血管疾病。

DESCRIPTION (provided by applicant): This K07 Career Development Award is intended to assist me in achieving my long-term goal of becoming an independent and productive exercise interventionist for cancer populations, who is able to build and lead transdisciplinary research teams to better cancer survivorship outcomes. My immediate goals are to utilize this award to acquire in-depth training in fields related to breast cancer survivorship, 1) by advancing my skills in exercise physiology to encompass cancer populations, 2) by obtaining further training in the design and execution of clinical trials in cancer populations necessary to become an independent academic investigator, 3) by executing this proposal to develop my independent line of research, and 4) by developing epidemiologic research findings into translatable intervention trials while participating in educational workshops and seminars within the Departments of Population Sciences, Medical Oncology, and Endocrinology at the City of Hope. The training and research I am proposing will allow me to develop an integrated understanding of epidemiology, health behavior, endocrinology, medical oncology, and breast physiology to better develop expertise in breast cancer survivorship research. The City of Hope National Medical Center (COHNMC) offers a wide breadth of resources and career development opportunities that will be utilized in this award. The COHNMC has been at the forefront of medical and basic science research since it was established in 1918. The COHNMC provides a vast environment with a vibrant long-standing history of high-quality research, which include key faculty members that will serve on my mentoring committee: Leslie Bernstein, PhD (primary mentor), Joanne Mortimer, MD (co-mentor), and Fouad Kandeel, MD, PhD (co-mentor). Therefore, fundamental departments at the COHNMC are highly involved in my career development plan including the Departments of Population Sciences (Bernstein), Medical Oncology and Therapeutics Research (Mortimer), and Diabetes, Endocrinology and Metabolism (Kandeel). Each department and associated mentor will provide unique and supple training opportunities that will be critical for the development of my career and will establish the groundwork as I become an independent cancer researcher. Breast cancer is a prevalent disease which due to medical and scientific advances has a high survival rate. However, serious breast cancer treatment side effects such as weight gain persist during survivorship and present an increased risk of developing metabolic-related diseases including diabetes and cardiovascular disease. The goal of the proposed research is to investigate the effects of an exercise intervention on metabolic syndrome (MetS) risk factors in pre- and postmenopausal breast cancer survivors. The objective is to improve survivorship utilizing an exercise intervention to diminish elevated components of MetS among breast cancer survivors. The first specific aim is to determine whether a 16-week exercise intervention will improve components of metabolic syndrome by measuring changes in body composition, waist circumference, blood pressure, resting energy expenditure (REE), and serum levels of insulin, glucose, lipids, and inflammatory markers. I will randomly assign 100 premenopausal and postmenopausal breast cancer survivors into either the Control or Exercise group for 16 weeks. The exercise intervention will include three weekly supervised exercise sessions including aerobic and resistance exercise. The second specific aim is to determine whether a 16-week exercise intervention will improve physical fitness in breast cancer survivors soon after completion of cancer-related treatments by measuring cardiorespiratory fitness and muscle strength. Finally, the third specific aim is to determine whether breast cancer survivors can maintain positive benefits of an exercise intervention following a 12-week follow-up period by measuring changes in body composition, waist circumference, blood pressure, and serum levels of insulin, glucose, lipids, C-reactive protein, and HbA1c, cardiorespiratory fitness and muscle strength. Following completion of the proposed research aims, it is expected that a 16-week exercise intervention performed soon after the completion of treatment will improve 1) components of metabolic syndrome and 2) physical fitness and strength among breast cancer survivors. These results will have a significant impact on cancer survivorship and disease risk following diagnosis and treatment. Survival rates for breast cancer are relatively high translating to a need for healthy living to diminish risk of other diseases such as diabetes and cardiovascular disease.