Diagnostic Value of Serum Concentration and Integrity of Circulating Cell-Free DNA in Breast Cancer: A Comparative Study With CEA and CA15-3.

Breast cancer (BC) is one of the most common types of malignant neoplasm in women; the incidence of BC increases yearly. In a previous study, a novel and sensitive method for quantitying cell-free DNA (CFD) in human blood was established and tested for its ability to predict which patients harbored tumors. Our objective in this study was to investigate the clinical value of serum concentration and the integrity of circulating free DNA (CFD) as a biomarker for auxiliary diagnosis of BC. The concentration of CFD was quantitated by branched DNA (bDNA)-based Alu assay. Carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) concentrations were determined via Abbott ARCHITECT I2000 SR testing. We report that the median (quartile interval) values of serum ALU115 and ALU247/115 in patients with BC were significantly higher than those in patients with benign mammary hyperplasia and in healthy control individuals (1083.66 ng/mL [1.81] vs 145.87 ng/mL [0.33] and 228.19 ng/mL [0.48]; P <.001); there was no significant difference between the latter 2 groups (P> .05). The cutoff values of ALU115, ALU247/115, CEA, and CA15-3 were set as 300.96 ng per mL, 0.78, 5 ng per mL, and 31.3 ng per mL, respectively. The area under the receiver operating characteristic (ROC) curve was 0.70 (95% confidence interval [CI], 0.58-0.81), 0.97 (<.001->.99), 0.75 (0.65-0.86), and 0.89 (0.82-0.96), respectively. Combined detection of the 4 indices significantly improved the diagnostic accuracy of BC, with sensitivity of 97.5% and negative predictive value of 96.4%. Also, serum ALU115 was significantly correlated with lymph-node metastasis (P = .048), and the ALU247/115 index was significantly correlated with tumor stage (P = .001) and lymph-node metastasis (P = .008) in patients with BC. Serum cell-free DNA (CFD) and its integrity may prove to be useful biomarkers for auxiliary diagnosis, grading of malignant neoplasms, and prognostic prediction of BC.