A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer

• We report a 1H NMR-based metabolic phenotyping study of breast cancer patients.
• Serum NMR metabolic profiles discriminate metastatic breast cancer from the localized early disease.
• Our model is validated with an independent cohort and provides high sensitivity and specificity.
• Nine statistically significant metabolites involved in this discrimination are identified.

Breast cancer (BC) displays a high heterogeneity from histology to prognosis, metastatic evolution and treatment responses. We report here a 1H NMR-based metabolic phenotyping study aiming at identifying coordinated metabolic serum changes associated with advanced metastatic breast cancer (MBC) in comparison to the localized early disease (EBC). A model discriminating EBC and MBC patients is obtained (n = 85: 46 EBC and 39 MBC), and validated with an independent cohort (n = 112: 61 EBC and 51 MBC; 89.8% sensitivity, 79.3% specificity). We identify 9 statistically significant metabolites involved in this discrimination: histidine, acetoacetate, glycerol, pyruvate, glycoproteins (N-acetyl), mannose, glutamate and phenylalanine. This work illustrates the strong potential of NMR metabolic phenotyping for the diagnosis, prognosis, and management of cancer patients.