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Grant Details

Grant Number: 5R21CA178359-02 Interpret this number
Primary Investigator: Demark-Wahnefried, Wendy
Organization: University Of Alabama At Birmingham
Project Title: Exploring Effects of Weight Loss on Ductal Carcinoma in Situ
Fiscal Year: 2015


Abstract

DESCRIPTION (provided by applicant): Obesity is a known risk factor for invasive breast cancers that occur post-menopause. Obese women also die twice as frequently from breast cancer than those of normal weight. Numerous preclinical studies show the benefits of caloric restriction on cancer progression in animals - but, will similar effects be seen in humans? In response to a call for translational studies that will identify biological/biobehavioral pathways through which weight loss may affect cancer prognosis (PAR-12-229), we propose a pilot study that builds on our success of pre-surgical interventions to answer the research question, "does negative energy balance with concomitant weight loss invoke anti-cancer effects on tumor biology and the host environment?" We will randomly assign 40 overweight or obese postmenopausal women diagnosed with ductal carcinoma in situ (DCIS) (a precursor to invasive cancer) who elect mastectomy or lumpectomy to 1-of-2 study arms: 1) an Attention Control Group that receives instruction on dietary approaches to correct nutritional deficiencies and progressive resistance training (PRT) that targets the arm ipsilateral to the affected breast; or 2 an Experimental Group that will receive PRT and guidance to correct nutritional deficiencies plus an intensive intervention to promote a 1.5-2 pound/week weight loss through diet, exercise, and behavior modification. This study will explore and contrast changes in body mass index (BMI) observed from enrollment to the time of surgery in the experimental vs. attention control arms, and also monitor changes in energy intake and physical activity. These changes will be studied in relation to the following endpoints: a) changes in select circulating biomarkers and gene expression related to cancer progression, hormonal status, inflammation and other energy-related factors; b) rates of tumor proliferation and apoptosis; c) tumor markers, e.g., insulin receptor, VEGF, AKT, NFkB, and phosphoproteins associated with the Convergence of Hormones, Inflammation and Energy-Rated Factors (CHIEF) pathway; and d) functional and health-related outcomes. Because both tumor tissue and blood will be examined from pre-to-post-intervention, this study will provide exciting new data that can elucidate pathways by which energy balance affects breast cancer progression from a non-invasive to an invasive state. Although longer term weight loss is recommended for overweight and obese breast cancer survivors, it is not known whether placing the body in a state of negative energy balance will have a favorable impact on the tumor. If beneficial changes in tumor biology and the host environment occur with short-term, pre-surgical weight loss, this study provides proof of concept that weight loss may offer an acceptable and complementary treatment option that could be combined with active surveillance for longer term management. Thus, the research that is proposed will not only increase our understanding of the impact of negative energy balance on tumor biology, but could change the standard of care and offer a more conservative treatment option for the 50,000 American women who are diagnosed with DCIS each year.



Publications

Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls.
Authors: Smith K.S. , Frugé A.D. , van der Pol W. , Caston N.E. , Morrow C.D. , Demark-Wahnefried W. , Carson T.L. .
Source: Beneficial microbes, 2021-06-15; 12(3), p. 239-248.
EPub date: 2021-04-01.
PMID: 33789551
Related Citations

Associations between Dietary Fiber, the Fecal Microbiota and Estrogen Metabolism in Postmenopausal Women with Breast Cancer.
Authors: Zengul A.G. , Demark-Wahnefried W. , Barnes S. , Morrow C.D. , Bertrand B. , Berryhill T.F. , Frugé A.D. .
Source: Nutrition and cancer, 2021; 73(7), p. 1108-1117.
EPub date: 2020-06-26.
PMID: 32590914
Related Citations

Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics.
Authors: Demark-Wahnefried W. , Rogers L.Q. , Gibson J.T. , Harada S. , Frugé A.D. , Oster R.A. , Grizzle W.E. , Norian L.A. , Yang E.S. , Della Manna D. , et al. .
Source: International journal of cancer, 2020-05-15; 146(10), p. 2784-2796.
EPub date: 2019-09-05.
PMID: 31442303
Related Citations

Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial.
Authors: Frugé A.D. , Van der Pol W. , Rogers L.Q. , Morrow C.D. , Tsuruta Y. , Demark-Wahnefried W. .
Source: Journal of the Academy of Nutrition and Dietetics, 2020 04; 120(4), p. 650-659.
EPub date: 2018-11-09.
PMID: 30420171
Related Citations

Exploring effects of presurgical weight loss among women with stage 0-II breast cancer: protocol for a randomised controlled feasibility trial.
Authors: Tsuruta Y. , Rogers L.Q. , Krontiras H. , Grizzle W.E. , Frugé A.D. , Oster R.A. , Umphrey H.R. , Jones L.W. , Azrad M. , Demark-Wahnefried W. .
Source: BMJ open, 2016-09-15; 6(9), p. e012320.
EPub date: 2016-09-15.
PMID: 27633639
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