Exploring the Clinical Transformation of circRNA as a Biomarker in Breast Cancer.

This narrative review systematically examines the potential of circular RNAs (circRNAs) as clinical biomarkers in breast cancer, focusing on the translational gap between basic discoveries and clinical applications. circRNAs are covalently closed non-coding RNA molecules characterized by high stability and tissue-specific expression, making them promising candidates for liquid biopsy. In breast cancer, a highly heterogeneous disease, circRNA expression profiles exhibit subtype-specific patterns and are associated with tumorigenesis, progression, and therapeutic resistance. Mechanistically, circRNAs function as microRNA sponges, interact with RNA-binding proteins, and can even encode functional polypeptides, thereby influencing cancer stem cell properties, immune escape, and organ-specific metastasis. Tumor-derived extracellular vesicles (EVs) carry circRNA signatures that offer a novel source for non-invasive biomarker detection. However, clinical translation is hindered by challenges in detection standardization, functional validation, and a lack of prospective, large-cohort studies. This review critically evaluates the biological functions and clinical relevance of circRNAs, discusses the role of EV-derived circRNAs in metastasis monitoring, and outlines a roadmap to overcome current translational bottlenecks, ultimately assessing their potential as diagnostic, prognostic, and predictive tools in breast cancer management.