Abstract B130: Adiposity-related metabolomic signatures and mortality in a population-based cohort of Black breast cancer survivors

Abstract Background: Black women in the U.S. experience higher mortality following a breast cancer (BC) diagnosis than other racial and ethnic groups, partly due to a greater prevalence of obesity. However, the metabolic pathways linking adiposity to mortality after BC diagnosis remain unclear, and distinct metabolic signatures associated with specific adiposity measures, such as central adiposity, warrant further investigation. We aimed to identify adiposity-related metabolites associated with all-cause mortality in a large population-based cohort of Black BC survivors. Methods: In the Women's Circle of Health Follow-up Study, untargeted metabolomic profiling was performed on plasma samples from Black BC survivors (n = 603), collected ∼2 years post-diagnosis. Each log-transformed metabolite was scaled to standard deviation units. Partial Pearson correlations were used to identify metabolites associated with any of the five adiposity measures assessed at the time of blood collection: BMI, waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and lean mass index. Metabolites meeting both the Bonferroni-corrected p-value threshold (p < 0.00001) and a correlation coefficient (|r| > 0.15) were subsequently evaluated for associations with all-cause mortality (82 deaths) using multivariable-adjusted Cox proportional hazards models, with statistical significance defined as a false discovery rate < 0.05. Results: Among 805 named metabolites, 109 were associated with adiposity measures, and 11 of these were also significantly associated with all-cause mortality. Higher levels of metabolites indicative of greater adiposity, including those involved in carbohydrate metabolism [glucose (more strongly associated with WC and WHR than with BMI), mannose, and N-acetylglucosamine/N-acetylgalactosamine], lipid metabolism [glycerol, 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6)], and secondary bile acid metabolism [glycoursodeoxycholic acid sulfate (1)], as well as N6-carbamoylthreonyladenosine and C-glycosyltryptophan, were positively associated with mortality, with HRs ranging from 1.31 to 1.60. Additionally, three metabolites that were inversely correlated with adiposity measures—asparagine (more strongly with WC, WHR, and FMI than with BMI), 1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6), and the xenobiotic 4-hydroxychlorothalonil, a metabolite that may interact with gut microbiome—were inversely associated with mortality, with HRs ranging from 0.66 to 0.71. Conclusions: Our study identifies specific adiposity-related metabolomic signatures associated with mortality risk, including those linked to central adiposity, among Black BC survivors. These metabolites provide insights into underlying metabolic mechanisms and may inform future research and interventions to improve survival in this high-risk population. Citation Format: Bo Qin, Shromona Sarkar, Sneha Manikandan, Tengteng Wang, Nur Zeinomar, Mi-Hyeon Jang, Coral Omene, Steven C. Moore, Chi-Chen Hong, Elisa V. Bandera. Adiposity-related metabolomic signatures and mortality in a population-based cohort of Black breast cancer survivors [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B130.