A novel serum metabolome score for breast cancer diagnosis

Early detection of breast cancer is important in diagnosis and treatment, and so in enhancing patient survival and reducing death rates. Because of the low diagnostic sensitivity and specificity of widely used breast cancer biomarkers such as CA15-3, we hypothesised that a panel of new metabolic markers would provide superior sensitivity and specificity for this disease.

We recruited 120 women with malignant breast cancer, 47 with benign breast disease and 55 females as a healthy control group. Metabolites 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine, and 1-methyl adenosine were detected and quantified by gas chromatography-mass spectrometry, CA15.3 by ELISA. Cut-off values of individual and combined metabolome with CA15-3 were analysed using the receiver operating characteristics curve (ROCC) to test the efficiency of the candidate metabolome in identifying breast cancer.

The overall linear trend of biomarkers across the groups was significant with highest levels in breast cancer (all p < 0.05). Using cut-off values of CA15-3, 8-hydroxy-2'-deoxyguanosine, 1-methylguanosine and 1-methyl adenosine of 30.5 U/l, 15.0 µg/l, 18.5 µg/l and 22.0 µg/l, respectively, diagnostic performance analyses of combined metabolome with CA15-3 gave a ROCC area under the curve of 0.94 (95% CI: 0.91-0.98)(p < 0.01) with good sensitivity (88.8%), specificity (86.8%) and efficiency (90.6%). Unlike CA15.3, the highest levels of each of the metabolite were in the early stage of breast cancer.

The diagnostic combination test of candidate metabolome with CA15.3 may be a useful tool for the early detection of breast cancer and used as a metabolomics signature in this disease.