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.

Over the years, we have witnessed a dramatic rise in the number of breast cancer survivors in the United States, which may be a reflection of increasing incidence, early detection and improved treatments. I hope to determine positive benefits of exercise to improve body weight, blood pressure, and blood lipids, as a means to improve survivorship. Such a lifestyle strategy would have a profound impact on the entire community of breast cancer survivors.