Stephen D. Hursting, PhD, MPH

2012-2013 BCRF Project:
(made possible by generous support from ANN INC.)

Excess endogenous insulin, insulin-like growth factor (IGF)-1, estradiol (E2), and inflammatory factors are involved in promotion of breast cancer in overweight and obese women, who make up 2/3 of the US adult population. Building on his previous studies on breast cancer prevention in women at high risk because of obesity, Dr. Hursting plans to augment the effects of dietary weight loss regimens on breast cancer risk with high dose omega-3 fatty acids.

Dr. Hursting’s team has recently completed a successful pilot of a weight loss intervention (via low-calorie diet) in postmenopausal women in which a median 11% weight loss over six months was associated with decrease in multiple serum and tissue risk biomarkers for breast cancer. They are currently completing pilot studies in pre- and postmenopausal women, and in ER-negative and ER-positive laboratory models of breast cancer, treated with high dose omega-3 fatty acid, which has been shown to decrease insulin resistance in animal model studies by reducing inflammation caused by macrophage infiltration and adipocyte secretion of cytokines. Preliminary results indicate that an effective dose of the fatty acids (using the commercially available product Lovaza®) is associated with reduction in proliferation and improvement in cytomorphology in pre- and postmenopausal women. Blood and tissue based measures of microRNAs (miRs, which regulate the expression of many genes) associated with cancer development as well as tissue associated measures of inflammation (particularly those associated with macrophage infiltration) are pending conclusion of the trial, although preliminary data from laboratory studies suggest weight loss is associated with changes in several miRs.

Dr. Hursting’s team plans to conduct an additional laboratory study to compare weight loss by total calorie restriction (CR), carbohydrate restriction (an approach that may be more readily adopted than CR by women to reduce weight), high dose omega-3 FA, or the combination of CR + the omega-3’s or carbohydrate restriction with omega-3’s. This study will parallel a clinical trial directed by fellow BCRF grantee, Carol Fabian, MD (University of Kansas Medical Center) studying dietary weight loss, omega-3 FAs or the combination, in overweight women over 40 years of age, to determine feasibility in terms of tolerance and biomarker assessment.

Mid-year Progress: Dr. Hursting's team is extending their previous BCRF-funded work by conducting a study in their MMTV-Wnt-1 transgenic laboratory model of ER-negative breast cancer comparing: 1) a low calorie diet; 2) a carbohydrate restricted diet; 3) Lovaza®; 4) the combination of low calorie diet plus Lovaza®; or 5) the combination of carbohydrate restriction plus Lovaza®, in obese models. Initial findings suggest that the omega-3 fatty acids augment the low calorie diet (no data yet on the carbohydrate restricted diet) and effectively decrease tumor development, normalize metabolic hormone levels and decrease inflammation. This study parallels a clinical trial directed by fellow grantee Dr. Carol Fabian, MD studying dietary weight loss, Lovaza® or the combination, in overweight women to determine the feasibility of a large-scale clinical trial of a combined weight loss and omega-3 fatty acid intervention.

Bio:
Dr. Stephen D. Hursting is Professor and Chair of the Department of Nutritional Sciences, as well as the Margaret McKean-Love Chair of Nutritional, Molecular and Cellular Sciences, at the University of Texas at Austin. He is also Professor of Carcinogenesis at the UT-MD Anderson Cancer Center. Dr. Hursting earned his PhD in nutritional biochemistry and MPH in nutritional epidemiology from the University of North Carolina at Chapel Hill, and he completed postdoctoral training in molecular carcinogenesis and cancer prevention as a Cancer Prevention Fellow at the NCI. Prior to joining the University of Texas faculty, Dr. Hursting was Chief of the NCI's Nutrition and Molecular Carcinogenesis Laboratory Section and Deputy Director of the NCI's Office of Preventive Oncology (1999-2005).

Dr. Hursting's research interests center on diet-gene interactions relevant to cancer prevention, particularly the molecular and hormonal mechanisms underlying energy balance-breast cancer associations. His research program, which has resulted in more than 125 peer-reviewed publications, focuses on three interrelated areas: 1. mechanism-based nutrition and cancer prevention studies in genetically engineered mice; 2) molecular and metabolic mechanisms underlying the energy balance and carcinogenesis relationship, with a particular interest in the roles of the IGF-1/Akt/mTOR signaling pathways and inflammatory pathways in breast and pancreatic cancers; and 3) translational nutrition and chemoprevention studies linking preclinical research with complementary clinical or epidemiologic studies.