Plasma cell-free DNA biomarkers as novel diagnostic and prognostic tools in breast cancer

Breast cancer remains the leading cause of cancer-related deaths among women, underscoring the need for more sensitive and specific biomarkers. Traditional markers such as CA15-3 lack sufficient diagnostic and prognostic accuracy. Quantification of plasma cell-free DNA (cfDNA) offers a minimally invasive liquid-biopsy approach for tumor detection and monitoring. This case-control study assessed a cfDNA panel comprising KLK10, SOX17, WNT5A, and MSH2 in 100 breast cancer patients and 100 matched controls. Plasma cfDNA levels, quantified by qPCR, and CA15-3 levels, measured by ELISA, were evaluated for diagnostic and prognostic value using ROC analyses and a 35-month follow-up for survival endpoints. All cfDNA genes were significantly elevated in patients (p<0.001) and exhibited superior diagnostic accuracy versus CA15-3, with MSH2 showing the highest AUC (95.3%), sensitivity (92%), and specificity (89%). Elevated cfDNA correlated strongly with metastasis and adverse pathological features, outperforming CA15-3 in predicting metastasis (AUC = 0.962-0.987). High cfDNA concentrations associated with poorer disease-free and overall survival (p<0.001). Detection of a cfDNA panel, rather than a single gene, demonstrates superior utility as a minimally invasive biomarker promising for early detection, risk assessment, and disease monitoring in breast cancer.