Nevertheless, DKK3 promoter methylation could exhibit the feasibility to detect cfDNA methylation of smaller tumors (pT1-2), which also remains valid in combination with ITIH5. ROC analysis of cfDNA methylation of pT1-2 tumors increased the sensitivity of the DKK3 and ITIH5 gene combination in the validation set from 40% to 43% (AUC, 0.688 (95% CI, 0.624 to 0.752)), which might indicate a potential benefit of DKK3 and ITIH5 for the early detection of breast cancer. This evidence concerns the gene ITIH5 and breast cancer.