Table 4.

Projects in the University of Pennsylvania TREC Survivor Center (Principal Investigator: Kathryn Schmitz, PhD, MPH)

Project 1: Impact of Exercise and Caloric Restriction on Cancer Recurrence in Mice. Project leader: Lewis Chodosh, MD, PhD Project 1 will use an innovative genetically engineered mouse model for breast cancer recurrence to determine the direct effects of exercise, calorie restriction, or their combination on breast cancer recurrence and surrogate biomarkers of recurrence risk. Mammary tumors will be induced in overweight mice by the doxycycline-dependent activation of an oncogene relevant to human breast cancer in the mammary glands of mice fed a high fat diet. Regression of the resulting tumors will be induced by oncogene down-regulation to generate cohorts of mice bearing dormant residual tumor cells. Overweight mice bearing residual disease will be randomly assigned to exercise, caloric restriction, both of these interventions, or neither and followed for cancer recurrence. Biomarkers will be evaluated to explore the hypothesized relationship between energy balance and recurrence and will include markers reflecting the PI3K-Akt-mTOR pathway, insulin resistance, IGF-1, HGF, adipokines, inflammation, tumor angiogenesis and oxidative stress.

Project 2: Women In Steady Exercise Research (WISER) Survivor Trial. Project Leader: Kathryn Schmitz, PhD, MPH The WISER Survivor Trial is a follow-on to the WISER Trial from TREC1 [35-38], the ongoing WISER Sister Trial (R01-CA131333 to Schmitz), and the PAL trial [39,40]. The goals of the WISER Survivor trial are to assess the effects of exercise and/or weight loss through caloric restriction on a common long term adverse effect of treatment (lymphedema), biomarkers for recurrence, and quality of life. Blood samples will be stored until results from project 1 are available. Surrogate biomarkers for the molecular pathways that mediate observed effects in project 1 will be analyzed. This one year controlled weight loss and exercise intervention trial will randomize a multi-ethnic cohort of overweight and obese breast cancer survivors with clinically confirmed lymphedema into four groups: exercise, caloric restriction, both of these interventions, or neither (control group), with a sample size of 125 per group (N=500).

Project 3: Breast Cancer-Related Lymphedema: Cost of Illness and Cost Effectiveness of Alternative Management Strategies. Project leader: J. Sanford Schwartz, MD Breast cancer related lymphedema (BCRL), characterized by arm swelling, impaired function and bothersome symptoms, is a common, persistent adverse event of breast cancer therapy. BCRL incurs substantial health care costs (significant portions of which are borne by patients), reduces productivity and reduces quality of life. Effective behavioral interventions such as exercise training and weight loss may mitigate its impact and prevent progression, but often are not reimbursed. There is a compelling need to better characterize the medical economic impact of BCRL, as well as its short– and long–term health consequences. Project 3 will: (1) assess BCRL direct medical care costs; (2) assess the incremental cost–effectiveness of the Project 2 interventions; and (3) model the impact of the Project 2 interventions over an extended time frame.