Circulating Non-Coding RNAs as Liquid Biopsy Biomarkers for Early Detection of Triple-Negative Breast Cancer: From Diagnostic Performance to Clinical Translation
Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive and molecularly heterogeneous breast cancer subtype for which early detection remains clinically important. Circulating non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are being investigated as blood-based biomarkers. This narrative review evaluates the clinical evidence for circulating ncRNAs as liquid-biopsy biomarkers for early TNBC detection, focusing on stage I–II disease, diagnostic performance, comparator selection, and validation. Methods: Peer-reviewed studies published between 2009 and October 2026 were identified primarily through PubMed/MEDLINE searches, supplemented by Google Scholar searches, with particular attention to disease stage, comparator populations, diagnostic performance, and validation status. Results: Among the ncRNA classes reviewed, circulating miRNAs provide the most directly relevant, although still limited, clinical evidence for early-stage TNBC detection, whereas evidence for lncRNAs and circRNAs remains predominantly exploratory and insufficiently validated for early-stage detection. Translation is limited by small, heterogeneous cohorts, analytical variability, and insufficient independent and prospective validation. Conclusions: High diagnostic accuracy in selected cohorts does not establish clinical readiness. Standardized analytical workflows, independent multicenter validation, prospective evaluation in intended-use populations, and integration with imaging and clinical assessment are needed before circulating ncRNA signatures can be considered for clinical use.
Authors
- Tsonka Slavova Dimitrova (ORCID: https://orcid.org/0000-0002-8796-7155)
- M Tsvetkova (ORCID: https://orcid.org/0000-0001-8377-595X)
- Galina Aleksieva Yaneva (ORCID: https://orcid.org/0000-0002-6194-2902)
- Ivaila Kuleva (ORCID: https://orcid.org/0000-0002-3424-202X)
- Stoyan Stoyanov (ORCID: https://orcid.org/0009-0000-7441-2057)
- Nikoleta Ivanova (ORCID: https://orcid.org/0000-0001-9241-4304)
- Dzheni Cherneva
Institutions
- Medical University of Varna (BG)
Publication Details
- Journal
- Diagnostics
- Published
- 2026-10-30
- DOI
- https://doi.org/10.3390/diagnostics16213591
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00