A plasma metabolite panel as biomarkers for early primary breast cancer detection

In recent years, metabolites have attracted substantial attention as promising novel biomarkers of various diseases. However, breast cancer plasma metabolite studies are still in their infancy. Here, we investigated the potential of metabolites to serve as minimally invasive, early detection markers of primary breast cancer. We profiled metabolites extracted from the plasma of primary breast cancer patients and healthy controls using tandem mass spectrometry (UHPLC-MS/MS and FIA-MS/MS). Two metabolites were found to be upregulated, while 16 metabolites were downregulated in primary breast cancer patients compared to healthy controls in both the training and validation cohorts. A panel of seven metabolites was selected by LASSO regression analysis. This panel could differentiate primary breast cancer patients from healthy controls, with an AUC of 0.87 (95% CI: 0.81 similar to 0.92) in the training cohort and an AUC of0.80 (95% CI: 0.71 similar to 0.87) in the validation cohort. These significantly differentiated metabolites are mainly involved in the amino acid metabolism and breast cancer cell growth pathways. In conclusion, using a metabolomics approach, we identified metabolites that have potential value for development of a multimarker blood-based test to complement and improve early breast cancer detection. The panel identified herein might be part of a prescreening tool, especially for younger women or for closely observing women with certain risks, to facilitate decision making regarding which individuals should undergo further diagnostic tests. In the future, the combination of metabolites and other blood-based molecular marker sets, such as DNA methylation, microRNA, and cell-free DNA mutation markers, will be an attractive option. What's new? While alterations in metabolite levels offer valuable insight into molecular and pathological events, their utility as biomarkers in cancer has not been fully explored. Here, circulating free metabolites in blood were investigated for their ability to serve as biomarkers in breast cancer. Out of 18 metabolites that varied significantly between primary breast cancer patients and healthy controls, seven showed superior discriminatory accuracy. Pathway analyses indicated that the seven metabolites function primarily in amino acid metabolism and breast cancer cell growth. The findings open the way for the development a blood-based test for breast cancer detection that incorporates multiple metabolite markers.