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

这个K07职业发展奖旨在帮助我实现我的长期目标，成为癌症人群的独立和富有成效的运动干预者，能够建立和领导跨学科的研究团队，以更好的癌症生存结果。我的近期目标是利用这个奖项获得与乳腺癌生存相关领域的深入培训，1）通过提高我在运动生理学方面的技能，以涵盖癌症人群，2）通过获得进一步的培训，在癌症人群中设计和执行临床试验，成为独立的学术研究者，3）通过执行这个建议，发展我的独立研究路线，以及4）通过将流行病学研究结果转化为可翻译的干预试验，同时参加City of Hope的人口科学，医学肿瘤学和内分泌学部门的教育讲习班和研讨会。我所建议的培训和研究将使我能够对流行病学、健康行为学、内分泌学、医学肿瘤学和乳腺生理学有一个综合的理解，从而更好地发展乳腺癌生存研究的专业知识。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，将在这个奖项中使用。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，拥有充满活力的长期高质量研究历史，其中包括将在我的指导委员会任职的关键教师：Leslie伯恩斯坦，博士（主要导师），Joanne Mortimer，MD（共同导师）和Fouad Kandeel，MD，博士（共同导师）。因此，COHNMC的基础部门高度参与了我的职业发展计划，包括人口科学部门（伯恩斯坦），医学肿瘤学和治疗研究部门（莫蒂默），糖尿病，内分泌学和代谢部门（坎德尔）。每个部门和相关的导师将提供独特和灵活的培训机会，这将是我的职业生涯的发展至关重要，并将建立基础，因为我成为一个独立的癌症研究人员。乳腺癌是一种流行病，由于医学和科学的进步，其生存率很高。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，并增加了发展代谢相关疾病的风险，包括糖尿病和心血管疾病。这项研究的目的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。其目的是提高生存率，利用运动干预，以减少乳腺癌幸存者中代谢综合征的升高成分。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）和胰岛素、葡萄糖、脂质和炎症标志物的血清水平的变化，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有监督的运动，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功能和肌肉力量来确定16周的运动干预是否会在完成癌症相关治疗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、血压和胰岛素、葡萄糖、血脂、C反应蛋白和HbA1c的血清水平、心肺功能和肌肉力量的变化，确定乳腺癌幸存者是否可以在12周的随访期后保持运动干预的积极益处。 在完成拟议的研究目标后，预计在治疗完成后不久进行的16周运动干预将改善1）代谢综合征的组成部分和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生存率和疾病风险产生重大影响。乳腺癌的生存率相对较高，这意味着需要健康的生活来减少其他疾病的风险，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.