{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:24:47Z","timestamp":1791923087480,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID FONDAP","award":["152220002"],"award-info":[{"award-number":["152220002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype, with limited diagnostic options and no targeted early detection tools. Liquid biopsy represents a minimally invasive approach for detecting tumor-derived molecular alterations in body fluids. This scoping review aimed to comprehensively synthesize all liquid biopsy-derived molecular biomarkers evaluated for the diagnosis of TNBC in adults. Methods: This review followed the Arksey and O\u2019Malley framework and PRISMA-ScR guidelines. Systematic searches of PubMed, Scopus, Embase, and Web of Science identified primary human studies evaluating circulating molecular biomarkers for TNBC diagnosis. Non-TNBC, non-human, hereditary, treatment-response, and nonmolecular studies were excluded. Data on study design, patient characteristics, biospecimen type, analytical platforms, biomarker class, and diagnostic performance were extracted and synthesized descriptively by biomolecule class. Results: Thirty-two studies met the inclusion criteria, comprising 15 protein-based, 12 RNA-based, and 6 DNA-based studies (one reporting both protein and RNA). In total, 1532 TNBC cases and 3137 participants in the comparator group were analyzed. Protein biomarkers were the most frequently studied, although only APOA4 appeared in more than one study, with conflicting results. RNA-based biomarkers identified promising candidates, particularly miR-21, but validation cohorts were scarce. DNA methylation markers showed promising diagnostic accuracy yet lacked replication. Most studies were small retrospective case\u2013control designs with heterogeneous comparators and inconsistent diagnostic reporting. Conclusions: Evidence for liquid biopsy-derived biomarkers in TNBC remains limited, heterogeneous, and insufficiently validated. No biomarker currently shows reproducibility suitable for clinical implementation. Robust, prospective, and standardized studies are needed to advance liquid biopsy-based diagnostics in TNBC.<\/jats:p>","DOI":"10.3390\/diagnostics16020360","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:52:38Z","timestamp":1769190758000},"page":"360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Liquid Biopsy-Based Biomolecular Alterations for the Diagnosis of Triple-Negative Breast Cancer in Adults: A Scoping Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Orieta","family":"Navarrete-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Universidad de La Frontera, Programa de Doctorado en Ciencias M\u00e9dicas, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5976-0325","authenticated-orcid":false,"given":"Eddy","family":"Mora","sequence":"additional","affiliation":[{"name":"Universidad de Santiago de Chile, Postgrado de Anatom\u00eda Patol\u00f3gica, Santiago 8370003, Chile"},{"name":"Instituto de Investigaciones M\u00e9dicas y Biotecnol\u00f3gicas, Universidad de Carabobo (IIMBUC), Valencia 2001, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-252X","authenticated-orcid":false,"given":"Josue","family":"Rivadeneira","sequence":"additional","affiliation":[{"name":"Universidad de La Frontera, Programa de Doctorado en Ciencias M\u00e9dicas, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Herrera","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico F\u00e9lix Bulnes, Unidad de Patolog\u00eda Mamaria, Santiago 9110056, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-3338","authenticated-orcid":false,"given":"\u00c1ngela L.","family":"Riffo-Campos","sequence":"additional","affiliation":[{"name":"Universidad de La Frontera, Department of Chemical Engineering, Temuco 4780000, Chile"},{"name":"Center for Cancer Prevention and Control (CECAN), Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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