Clinical Relevance of Circulating Biomarkers in Breast Cancer Metastasis Detection: Insights From Liquid Biopsy Technology Publisher



Salimi Z ; Fatehifard R ; Aghaei M ; Panjehpour M
Source: Research in Pharmaceutical Sciences Published:2025

Abstract

Background and purpose: Breast cancer is a major global concern, especially because of high mortality linked to advanced stages. Metastasis may occur early, but current diagnostics struggle to detect small metastatic cells. Non-invasive liquid biopsies, such as circulating miRNA, ctDNA, and cfDNA, present a promising solution for screening and monitoring breast cancer. This study aimed to examine the clinical relevance of circulating levels of cfDNA, miR-182, CYFRA21-1, and CEA in metastatic and non-metastatic breast cancer patients and their association with clinical stage and distant metastasis. Experimental approach: Ten mL blood samples were collected from 17 metastatic and 29 non-metastatic breast cancer patients pre-surgery. cfDNA was measured fluorometrically, miRNA-182 via quantitative real-time PCR, CYFRA21-1, and CEA using enzyme-linked immunosorbent assay ELISA. Findings/Results: Results demonstrated significantly higher levels of cfDNA, miR-182, CYFRA21-1, and CEA in women with metastatic breast cancer compared to those with non-metastatic breast cancer. These markers were linked to advanced clinical stages and increased tumor size. Elevated levels of cfDNA, miR-182, and CYFRA21-1 were indicative of a higher risk for lymphatic metastasis, while cfDNA and CYFRA21-1 were associated with distant metastasis. ROC curve analyses revealed strong efficacy for cfDNA (AUC 0.94), miR-182 (AUC 0.91), CYFRA21-1 (AUC 0.88), and CEA (AUC 0.87) in detecting metastatic breast cancer. Conclusion and implications: Combined analysis of these biomarkers will enhance the predictive accuracy of metastatic breast cancer and clarify the relationship between biomarker profiles and the characteristics of metastatic versus nonmetastatic patients using liquid biopsy technology. © 2025 Elsevier B.V., All rights reserved.