Abstract LB-193: Prediagnostic breast cancer metabolites in Mexican Americans: a nested case control study
Authors: Strom Sara S. , Zhao Hua , Brewster Abenaa , Yamamura Yuko 
Published: August 2015

Abstract
Breast cancer (BrCa) is the most common invasive cancer in Hispanic women. Although at decreased risk, Hispanic women are diagnosed at younger ages and with more aggressive disease than non-Hispanic Whites. Early detection is key in BrCa survival; however, there are no pre-diagnostic circulating biomarkers for early detection. This pilot nested case-control study based on our Mexican-American Cohort (MAC) study evaluates the role of global metabolic expression in predicting BrCa risk. MAC includes ∼23,000 participants in the Houston area with baseline blood specimens and epidemiological data. Using mass spectrometry-based global protein expression, 435 plasma metabolites were analyzed by Metabolon in 30 invasive BrCa cases (14 pre- (preM) and 16 post-menopausal (postM)) diagnosed 1-5 years after enrollment and 40 healthy controls (matched to cases on age, menopausal status) and length of follow-up). Mean age of preM women was 37.6 years (range 32-43) compared to 63.4 for postM (range 50-81). Using principal component analysis, we evaluated differences by disease and menopausal status. We found 76 metabolites that differed significantly (P&lt;0.05) between cases and controls among postM women compared to only 13 metabolites in preM women. Using a pathway-based approach, we found that the majority of case-control differences were in metabolites related to hormone, lipid and energy metabolism. The specific metabolites differed by menopausal status. In postM cases, levels of steroid hormones epiandrosterone sulfate, androsterone sulfate, and 5-alpha-androstan-3beta,17beta-diol disulfate were higher than in controls; among preM cases, steroid hormones 5-alpha-pregnan-3beta,20alpha-diol disulfate and 5-alpha-pregnan-3alpha,20beta-diol disulfate 1 levels were higher. PostM cases had significantly (P&lt;0.05) lower levels in fatty acids valerylcarnitine and butyrylcarnitine and higher levels of monoacylglycerols and glycerol 3-phosphate (G3P) than controls; there were no significant differences in these metabolites in preM cases and controls. The statistically significant (P&lt;0.05) decreases in 3-phosphoglycerate, pyruvate, sarcosine (N-methylglycine), citrate, and malate which are all associated with glycolysis and the tricarboxylic acid cycle found in cases compared to controls irrespective of menopausal status, suggest energy metabolism may be associated with BrCa risk. In summary, our findings suggest: (1) case-control differences in plasma levels of specific metabolites associated with key functional pathways; (2) the specific metabolites and number of relevant metabolites differs by menopausal status; and (3) these differences are detectable years prior to diagnosis. Future studies exploring these associations with tumor hormone receptor status, dietary intake and anthropometric measurements will aid in further identifying key pre-diagnostic plasma markers for BrCa.
Citation Format: Sara S. Strom, Hua Zhao, Abenaa Brewster, Yuko Yamamura. Prediagnostic breast cancer metabolites in Mexican Americans: a nested case control study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-193. doi:10.1158/1538-7445.AM2015-LB-193