Breast cancer is a complex disease and research as well as compliance may be more productive if combinations of dietary intervention strategies are utilized. For this study we combined consumption of the omega-3 fatty acid eicosapentaenoic acid (EPA) with two modes of calorie restriction. We utilized six groups of MMTV-Her2/neu mice to represent the approximately 20% of human breast cancers in which Her2/neu is over expressed and for which there are no known chemo-preventive agents available. Starting at 10 weeks of age half of the mice were fed a control diet composed of a modified AIN-93M formula with fat derived from soy oil. The other half consumed a diet with 71.75% of fat calories from EPA. Mice were further divided into ad libitum (AL), chronic calorie restricted (CCR) or intermittent caloric restricted (ICR) groups. AL groups (Control and EPA) received unrestricted access to their diets. CCR groups were given 75% of the total calories that the AL age-matched groups consumed. ICR groups were fed calories equal to 100% of the AL age-matched groups for three weeks followed by three weeks of calories equal to 50% of the AL age-matched groups. Supplemental vitamins and minerals were added to the food for the CCR ands ICR groups. The 6 week cycles of restriction and refeeding were maintained until the mice were 60 weeks of age or were euthanized due to MTs. Mice were weighed weekly and carefully examined for mammary tumors (MTs). Ad Lib Control (Con) and Ad Lib-EPA groups ate similar amounts and gained weight at similar rates. The body weights of the CCR-Con and CCR- EPA were also similar to each other. The ICR-EPA mice were slightly heavier (p<0.05) than the CCR-Con mice despite consuming similar quantities of food. MT incidence was lowest in the ICR-EPA group (15%) and highest in the AL-Con group (87%) while the AL-EPA, CCR-Con, CCR-EPA and ICR-Con had MT incidence rats of 63%, 47%, 40% and 59%, respectively The average survival until terminal end point was also longest in the ICR-EPA group at 59.2 weeks and shortest in the AL-Con group at 52.6 (P<0.0002). The average tumor burden was 0.98 grams for ICR-EPA mice and 1.78 grams for AL-Con mice but due to the very small number of MTs in the ICR-EPA group this was not a significant difference. Preliminary serum microarrays and LC-MS/MS analysis of mammary tissue indicate that EPA decreases proteins associated with inflammation and oxidative phosphorylation suggesting that NFkB may be down-regulated. Ongoing studies seek to better understand this mechanism. These results illustrate that MT inhibition is significantly increased when ICR and EPA are combined as compared to either intervention alone or no intervention. Understanding how this pathway is affected may aid in the development of drugs that could be used for breast cancer prevention.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1869. doi:10.1158/1538-7445.AM2011-1869