Sedentary Behavior and Breast Cancer: Interventions and Biomarkers

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DESCRIPTION (provided by applicant): This K07 proposal details a comprehensive program of training activities, mentorship, and research projects that will provide me with the support, knowledge, and skills to launch a career as an independent investigator focused on sedentary behavior and breast cancer. As demonstrated by my educational background, publication history, and research activities, I am dedicated to the field of health behavior, obesity, and cancer prevention and survivorship. I received my Ph.D. in Epidemiology and Psychology from Yale University and completed a postdoctoral fellowship in biobehavioral cancer prevention and control at the Fred Hutchinson Cancer Research Center. I have been conducting research at the Moores Cancer Center at the University of California, San Diego (UCSD) since 2009 and was appointed as Assistant Professor within the UCSD Department of Family and Preventive Medicine in 2013. Completion of this K07 will facilitate my transition to an independent investigator and position me to become a leader in the field of sedentary behavior and cancer. Sedentary behavior, which is physiologically and behaviorally distinct from physical activity, is an emerging area of research that is of growing interest to the cancer community. Research on the adverse health effects of excessive sitting is advancing quickly, with recent data showing that objectively-measured sedentary time is associated with increased breast cancer risk. More research is needed to understand the relationship between sedentary time and breast cancer and to determine whether reducing sedentary time could lower risk and/or improve survival. The proposed training plan will allow me to gain advanced knowledge and skills in: (1) development of sedentary behavior interventions, (2) assessment of sedentary behavior using established & emerging methods, (3) biological mechanisms linking sedentary and active behaviors with cancer, (4) advanced statistics for analysis of sedentary and activity data, and (5) leadership, grant-writing, and career development. UCSD is the ideal environment in which to pursue these goals due to its exceptionally strong group of lifestyle and cancer researchers, the availability o newly-formed interest groups focused on sedentary behavior and health, and the presence of an NCI-funded Transdisciplinary Research on Energetics and Cancer (TREC) Center. My primary mentor will be Dr. Bess Marcus, with co-mentorship provided by Drs. Simon Marshall and Ruth Patterson. Dr. Marcus is Chair of Family and Preventive Medicine at UCSD, has had continuous NIH funding for the past 25 years, and has an excellent track record of mentoring junior faculty. Dr. Marshall is Associate Professor of Family and Preventive Medicine at UCSD, has expertise in sedentary behavior research, and has mentored over 100 students, fellows, and junior faculty. Dr. Patterson is the PI of the UCSD TREC Center and has expertise in cancer biomarkers. Consultants will ensure that I achieve my training and research goals in the areas of sedentary behavior assessment (Dr. Jacqueline Kerr), biologic mechanisms linking sedentary behavior with cancer (Dr. Neville Owen), and advanced statistics (Dr. Loki Natarajan). The proposed research includes 2 distinct, but complementary activities. For Aim 1, I will conduct a pilot study examining interventions to reduce sedentary behavior. Aim 2 uses data from the UCSD TREC Center to examine the association of sedentary behavior with cancer-related biomarkers. Aim 1 (original research): To conduct a 2x2 randomized controlled pilot trial among 60 postmenopausal breast cancer survivors to determine the feasibility of 2 intervention strategies for reducing objectively- measured sedentary behavior. Specifically, I will examine (1) brief "standing breaks" to interrupt long bouts of sedentary time, (2) overall 25% reduction in sedentary time, (3) both in combination, and (4) usual care. Aim 2 (analysis of TREC data): To investigate the potential cancer-relevant benefits of reducing sedentary behavior by examining, among 340 overweight/obese breast cancer survivors, the effects of a behavioral weight loss intervention on sedentary behavior (which is specifically targeted in the intervention). We will also examine whether changes in sedentary behavior mediate the impact of the intervention on biomarker outcomes (i.e. markers of insulin resistance, chronic inflammation, and sex hormones). Aim 1 will enhance my skills in designing and conducting a pilot trial, and study findings will provide insight on reducing sedentary time among breast cancer survivors. Aim 2 will increase my understanding of biomarkers, enhance my statistical and writing skills, and provide novel data on the association of objectively measured sedentary time with cancer-related biomarkers. Taken together, the results of the proposed aims will inform an R01 proposal for a trial examining the efficacy of a sedentary behavior intervention to positively impact circulating biomarkers related to breast cancer prognosis. If funded, this K07 will build on my previous experience in physical activity while taking my career in an exciting new direction focused on sedentary behavior.