Plasma Exposome Analysis Uncovers Metabolic Pathway Alterations in Aggressive Breast Cancer Subtypes

In the U.S., racial disparities persist in breast cancer survival rates and aggressive breast cancer subtypes. Although the etiology of breast cancer remains poorly understood, social determinants of health and environmental factors have been associated with increased risk of breast carcinogenesis. Exposome and metabolomics analysis of human plasma may provide insights into the underlying mechanisms of breast cancer disparities by identifying exposure to environmental agents and the associated biological response. De-identified plasma samples from the Normal Breast Study (NBS) were used for untargeted metabolomics analysis, and peaks were matched with an in-house standard library of over 5000 compounds. Using MetaboAnalyst 6.0, univariate statistical analysis was conducted to identify metabolic profiles by reported race, breast cancer status, breast cancer subtype, and tumor grade. Furthermore, pathway enrichment analysis was conducted to identify how environmental compounds modulate endogenous metabolism in each population. Results showed alterations primarily in lipid metabolism, amino acid metabolism, one-carbon metabolism and caffeine metabolism associated with exposures to compounds such as plasticizers, pesticides, and tobacco.