A Low Carbohydrate Nutritional Program Improves Weight, Insulin, and Estrogenic Parameters in Obese Patients with Estrogen Receptor Positive Endometrial Cancer L.A. Rojas-Espaillat1,2,3, A. K. Krie2, Z.M. Weber,4 K. N. Bohlen1,2,3,Y. Hu,3,4 M.S. Fagerness1,2, N.L. Flier1,2, J. Kittelsrud1,2, E.A. Ehli, 4,5 and G. E. Davies3,4 1Avera Research Institute, Sioux Falls, SD, 2Avera Cancer Institute, Sioux Falls, SD, 3 University of South Dakota, Sioux Falls, SD 4 Avera Institute for Human Genetics, Sioux Falls, SD, 5 University of South Dakota, Vermillion, SD Background Results Results Obesity increases the risk of developing and dying from endometrial cancer.2 Prospective clinical studies have demonstrated development of endometrial pathology in 62% of patients with hyperestrogenism.3 High serum levels of insulin and co-factors have been related to cell proliferation and neoplastic transformation of the endometrium.4 Obesity induces these hormonal and metabolic imbalances, leading to the development and survivorship challenges in endometrial cancer patients.1, 5 This feasibility study evaluated whether a low carbohydrate, calorie restricted dietary intervention, could achieve weight loss and improvement of these endocrine and metabolic parameters in a group of obese postmenopausal endometrial cancers survivors. Statistically significant declines in total body weight, hormonal and inflammatory markers, and insulin and co-factors were observed. * * Objectives The mean weight loss was 18.0% after 15 weeks (p=6.45 x10-7), equivalent to 41.3 lbs per individual. The mean percentage of total body fat loss was 6.6%. Weight loss averaged 5.3 lbs/week in week 1 and 2.6 lbs/week in weeks 2 -15. C reactive protein (CRP) levels were not reduced at 15 weeks, however did show a 34.76% reduction (p=0.0106) when evaluated at the end of each subject’s active weight loss period. Determine if patients could comply with the dietary intervention and achieve weight loss. Evaluate efficacy of the dietary intervention on decreasing serum hormone levels. Evaluate efficacy of the dietary intervention on decreasing serum insulin co-factors and inflammatory markers. Conclusions A low carbohydrate dietary intervention can successfully be implemented in a group of overweight endometrial cancer survivors to achieve significant weight loss. A rapid and significant reduction in serum insulin, hormonal and inflammatory markers can be achieved with dietary intervention. These metabolic changes have the potential to positively impacting endometrial cancer development and survival. This feasibility study provides additional support for large and long term trials evaluating the role of carbohydrate restriction in endometrial cancer patients. Methods Protein Meal Product Replacements (0.5 g protein/lb actual body weight), <40 gm carbs, 800-1200 calories/day Weekly Session with Health Coach Medical Monitoring (brief physical exam) Labs every 2 weeks x 12 weeks, then every month Total serum estrogen, estrone and estradiol decreased by 23.1% (p=0.0068), 20.1% (p=0.0021) and 34.2% (p=0.0508) respectively after 15 weeks. References Nickles-Fader A, Nieves-Arriba L, Frasure H, et al: Endometrial cancer and obesity: Epidemiology, biomarkers, preventions and survivorship. Gynecol Oncol 114(2009) 121 – 127. Celle E, Walker-Thurmond K, Thun MJ, et al: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2005; 348: 1625-1638. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestins Intervention (PEPI) Trial. The Writing Group for The PEPI trial. JAMA 1996; 275:370-5. Talavera F, Reynolds RK, Roberts JA, et al: Insulin-like growth factor I receptors in normal and neoplastic human endometrium. Cancer Res. 1990; 50:3019-24 Key TJ, Pike MD,. The dose-effect relationship between “unopposed” estrogens and endometrial mitotic rated: its central role in explaining and predicting endometrial cancer risk. Br Jcancer 1988;57:205-12 Eligibility Criteria Early Stage ER+ endometrial & breast cancer survivors Postmenopausal BMI >28 Completed surgery & adjuvant chemotherapy No underlying inflammatory condition No treatment for diabetes Demographics N= 8 Mean (range) Age 59.8 (42-68) Weight (pre-diet) 231.6 (191.4-292.0) BMI (pre-diet) 39.3 (29.2-49.5) Weight Loss Period 23.5 weeks (15-35) Declines in fasting insulin level were 52% (p=0.00189) and 61% (p=0.00251) after weeks 3 and 15.