Plasma cell-free DNA integrity plus circulating tumor cells: a potential biomarker of no distant metastasis breast cancer

Cell-free DNA integrity (dig) is a promising diagnostic and prognostic biomarker in breast cancer. However, no specific study has evaluated the diagnostic ability of cfDI in patients with no distant metastasis breast cancer (no-MBC) and benign breast tumor (BBT) to date. We assessed the plasma cfDI of 84 patients with no-MBC and 30 patients with BBT using quantitative PCR and compared it with circulating tumor cells (CTCs) and carbohydrate antigen 153 (CA153). The no-MBC group had significantly lower mean cfDI (0.58) than the BBT group (0.74, p = 0.004). Subgroup analysis showed that decreased cfDI seem to be associated with risk factors such as age <45 years (mean cfDI = 0.52), triple-negative breast cancer (mean cfDI = 0.56), IC167 > 14% (mean cfDI = 0.57), tumor size > 2 cm (mean cfDI = 0.58), and positive lymph node status (mean cfDI = 0.56), but had no statistical significance. McNemar's test suggested that cfDI had stronger diagnostic power than CTCs, cfDNA concentration, or CA153 (p <0.001). Spearman's rho showed that the correlation coefficient between cfDI and CTCs was 0.278 (p = 0.04) in the no-MBC group. Receiver operating characteristic curve analysis also suggested that cfDI was superior to CTCs or CA153. Combined with CTCs, cfDI reduced the false positive rate from 50% to 10.71% and increased the area under the curve value from 0.66 to 0.68. Our results suggest that cfDI is a potential diagnostic biomarker of no-MBC. Using cfDI and CTCs as a combined diagnostic tool for no-MBC could improve diagnostic sensitivity and specificity but more samples will be needed.