Abstract 4230: Modulation of adiponectin and leptin levels in obese post-menopausal women after 6 months of a structured weight loss intervention, randomized to placebo or supplemental omega-3 fatty acids

Abstract

Abstract Background Obesity is a modifiable risk factor for breast cancer in the United States. While structured interventions can achieve short-term weight loss, this does not necessarily correlate with favorable modulation of risk biomarkers at the blood or breast tissue level. We combined a proven intervention (calorie-controlled meals, moderate exercise, and weekly group behavioral session) with daily omega-3 fatty acid supplementation to examine whether we could improve either weight loss and/or biomarker modulation in women who are at high risk for development of breast cancer. Methods 46 post-menopausal high-risk women with a BMI > 27 kg/m2 (median 31 kg/m2) had baseline blood collections and random periareolar fine needle aspiration (RPFNA) benign breast tissue sampling for biomarkers. Two weeks after starting the weight loss intervention, subjects received study agent, randomized 1:1 to placebo vs. supplementation with 2100 mg Eicosapentaenoic Acid (EPA) + 1050 mg Docosahexaenoic Acid (DHA) daily. After 6 months, blood and tissue sampling were repeated. Results 42 women completed the 6 month weight loss intervention with all but one achieving a weight loss (median relative weight loss 12%; range 0 to 23%). For the entire cohort, there were substantial and favorable changes in levels in serum of blood collected fasting for adiponectin (increase; p<0.01) and leptin (decrease, p<0.001), as well as the ratio of adiponectin to leptin (A:L, increase, p<0.001). The same effect for all three measures was observed in serum collected 2 hours after a standard meal; and for leptin and the A:L ratio in breast tissue also collected postprandial. When dichotomized to relative weight losses of <10% vs >10%, women with >10% loss had greater favorable modulations for leptin and the A:L ratio for fasting and non-fasting serum (<0.0001 for all) as well as breast tissue (p<0.004). There were no significant differences between groups of women dichotomized by whether they exhibited (or not) an increase in the ratio of EPA:DHA to arachidonic acid in erythrocyte phospholipids at 6 months. Conclusions These results demonstrate that the cytokines adiponectin and leptin, and the ratio of the two, are robust biomarkers for modulation in serum and breast tissue of women achieving a successful weight loss on a structured intervention trial.Supported by a grant from the Breast Cancer Research Foundation and pilot funds from National Cancer Institute Cancer Center Support Grant P30 CA168524. Citation Format: Bruce F. Kimler, Jennifer L. Nydegger, Amy L. Kreutzjans, Teresa L. Phillips, Kandy R. Powers, Jennifer R. Klemp, Debra K. Sullivan, Christie A. Befort, Susan E. Carlson, Stephen D. Hursting, Carol J. Fabian. Modulation of adiponectin and leptin levels in obese post-menopausal women after 6 months of a structured weight loss intervention, randomized to placebo or supplemental omega-3 fatty acids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4230. doi:10.1158/1538-7445.AM2017-4230