Abstract 1893: Consumption of oil derived from frying bacon increases breast cancer metastasis

Abstract

Abstract Breast cancer continues to be the most commonly diagnosed cancer among women, with the majority of mortality being associated with the metastatic spread of this disease. In terms of onset, genetic drivers such as mutations in BCR1/2 account for only ~10% of all cases. Thus, environmental factors, including the diet are significant contributors to breast cancer onset and progression. In this regard, elevated circulating cholesterol levels are associated with a poor prognosis, while cholesterol lowering medication (statins) appear protective. We have previously shown that a high cholesterol diet increased both primary tumor growth and metastasis in preclinical models. Interestingly, it was found that the metastatic effects of cholesterol were primarily mediated by its metabolite, 27-hydroxychoelsterol (27HC). In addition to its effects on cancer cells, 27HC also required neutrophils and gamma delta T cells for its pro-metastatic effects. Therefore, we hypothesized that the consumption of foods with high cholesterol, and potentially oxidized cholesterol products, promote breast cancer progression. Bacon is a common food in the US and is prepared by frying in its own fat. We mimicked the preparation process by using a controlled pan-frying procedure. The used oil was collected and processed into food pellets (5% lipid from bacon frying fat, 5% lipid from soybean oil). A control diet was formulated as 5% fat from rendered pork lard, 5% lipid from soybean oil. We also included a diet with no expected cholesterol, where fat content was matched with soybean oil (10%). In order to determine the relative contribution of cholesterol to observed changes in metastatic colonization and outgrown, we also included groups where mice were treated with ezetimibe, a cholesterol uptake inhibitor. Mice were placed on their respective diets for 4 weeks prior to intravenous engraftment with Met1 cancer cells. There were no significant differences in weight gain observed between the experimental groups. 5 weeks post-engraftment, metastatic burden was assessed by ex vivo imaging. Compared to the no cholesterol control diet, there was a significant increase in metastatic burden in the lard group. Intriguingly, the bacon oil diet increased metastatic burden compared to both the lard and no cholesterol groups, and this increase was attenuated when mice were treated with ezetimibe. Ongoing work is aimed at assessing the circulating cholesterol and oxysterol concentrations, and evaluating changes in the metastatic microenvironment between mice on the different diets. Collectively, this study indicates that while cholesterol consumption increases metastatic progression, its preparation prior to consumption can also have significant impacts. Our work provides further rationale for diets low in cholesterol for breast cancer patients. This work was supported by the grants from the NCI, AICR and DOD-BCRP to ERN, and Arnold O. Beckman Research Award to WGH. Citation Format: Cheng Chen, Joy J. Chen, Liqian Ma, William G. Helferich, Erik R. Nelson. Consumption of oil derived from frying bacon increases breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1893.