Understanding the biological mechanisms that underlie the anti-tumorigenic effects of calorie restriction and physical activity will likely be essential for translating laboratory advances in this field to the development of more effective strategies for preventing cancer in humans. The goal of Project 1 ofthe Penn TREC Survivor Center is to advance our understanding of the impact of energetics on breast cancer recurrence. Project 1 will use an innovative genetically engineered mouse model for breast cancer recurrence developed at Penn to determine the effects of exercise, calorie restriction, or their combination on breast cancer recurrence. Mammary tumors will be induced in oven/veight 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, calorie 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-mT0R pathway, insulin resistance, IGF-1, HGF, adipokines, inflammation, tumor angiogenesis and oxidative stress. To our knowledge, this study will be the first to explore the impact of exercise and calorie restriction on cancer recurrence in an animal model. The studies proposed in Project 1 build on the unique combination of strengths and expertise in cancer biology, obesity, endocrinology, and exercise physiology among researchers in the proposed Penn TREC Survivor Center. In addition, the design of this study closely parallels an analogous human trial proposed in Project 2. The assembled team of investigators will work jointly to create new experimental paradigms that integrate and move beyond discipline-specific approaches to address the role of energy balance in breast cancer recurrence. In doing so, this project will advance the mission ofthe Penn TREC Survivor center to promote transdisciplinary, translational science on energy balance and cancer survivorship.

Public Health Relevance

Exercise and weight control are hypothesized to reduce the risk of recurrence in cancer survivors. However, the mechanisms proposed to underlie this effect are unknown. Project 1 will use an innovative genetically engineered mouse model for breast cancer recurrence to test this hypothesis and to evaluate changes in biomarkers hypothesized to reflect causal pathways linking energy balance and recurrence.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA155850-02
Application #
8377467
Study Section
Special Emphasis Panel (ZCA1-SRLB-4)
Project Start
Project End
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$321,337
Indirect Cost
$93,526
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Schmitz, Kathryn H; Gehlert, Sarah; Patterson, Ruth E et al. (2016) TREC to WHERE? Transdisciplinary Research on Energetics and Cancer. Clin Cancer Res 22:1565-71
Rogers, Benjamin H; Brown, Justin C; Gater, David R et al. (2016) Association Between Maximal Bench Press Strength and Isometric Handgrip Strength Among Breast Cancer Survivors. Arch Phys Med Rehabil :
Mitchell, Jonathan A; Godbole, Suneeta; Moran, Kevin et al. (2016) No Evidence of Reciprocal Associations between Daily Sleep and Physical Activity. Med Sci Sports Exerc 48:1950-6
Zhang, Zi; Brown, Justin C; O'Malley Jr, Bert W et al. (2016) Post-treatment weight change in oral cavity and oropharyngeal squamous cell carcinoma. Support Care Cancer 24:2333-40
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2016) The muscle quality index and mortality among males and females. Ann Epidemiol 26:648-53
Dean, Lorraine T; Brown, Justin; Coursey, Morgan et al. (2016) Great expectations: racial differences in outcome expectations for a weight lifting intervention among black and white breast cancer survivors with or without lymphedema. Psychooncology 25:1064-70
Brown, Justin C; Harhay, Michael O; Harhay, Meera N (2016) Patient-reported versus objectively-measured physical function and mortality risk among cancer survivors. J Geriatr Oncol 7:108-15
Dean, Lorraine T; Kumar, Anagha; Kim, Taehoon et al. (2016) Race or Resource? BMI, Race, and Other Social Factors as Risk Factors for Interlimb Differences among Overweight Breast Cancer Survivors with Lymphedema. J Obes 2016:8241710
Pahwa, Avita K; Andy, Uduak U; Newman, Diane K et al. (2016) Noctural Enuresis as a Risk Factor for Falls in Older Community Dwelling Women with Urinary Incontinence. J Urol 195:1512-6
Haggerty, Ashley F; Huepenbecker, Sarah; Sarwer, David B et al. (2016) The use of novel technology-based weight loss interventions for obese women with endometrial hyperplasia and cancer. Gynecol Oncol 140:239-44

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