{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:23Z","timestamp":1792789043236,"version":"4.5.0"},"reference-count":193,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Faisal University","award":["KFU265053"],"award-info":[{"award-number":["KFU265053"]}],"id":[{"id":"https:\/\/ror.org\/00dn43547","id-type":"ROR","asserted-by":"crossref"}]},{"award":["KFU265053"],"award-info":[{"award-number":["KFU265053"]}],"id":[{"id":"https:\/\/ror.org\/00dn43547","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Breast cancer is a biologically heterogeneous disease that requires accurate diagnosis, risk stratification, treatment selection and longitudinal assessment. Conventional imaging and tissue biopsy remain the mainstays of clinical management. However, tissue sampling represents a specific anatomical site and time point, and may not reflect the molecular heterogeneity or evolution of disease. Liquid biopsy offers a minimally invasive complementary approach, analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles. Applications include molecular characterization, treatment-response assessment, resistance detection and minimal residual disease (MRD) evaluation, which are under investigation or in clinical use. Gene-expression profiles, mutational alterations and epigenetic marks can generate molecular signatures that offer further support for tumor classification and risk stratification, and have demonstrated clinical value in specific breast cancer populations. Advances in next-generation sequencing, digital PCR, proteomic analysis, and artificial intelligence have expanded the analytical capacity for detection and interpretation of circulating and tissue-derived biomarkers. However, biological heterogeneity, low abundance of circulating biomarkers, pre-analytical and analytical variability, standardization of assays and limited prospective evidence for some applications are still major barriers to clinical translation. In this review, we discuss the biological basis, detection technologies, clinical applications and limitations of liquid biopsies and molecular signatures in breast cancer, highlighting multi-omics integration and computational approaches. It distinguishes between promising analytical biomarkers and clinically validated applications and highlights the evidence and methodological needs for wider implementation in precision breast cancer care.<\/jats:p>","DOI":"10.3390\/cancers18193235","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:26:53Z","timestamp":1791458813000},"page":"3235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics and Liquid Biopsy Integration for Precision Stratification of Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9432-2763","authenticated-orcid":false,"given":"Dheeraj","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, JSS University, Noida 201301, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-4381","authenticated-orcid":false,"given":"Shriyansh","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida 203201, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-2508","authenticated-orcid":false,"given":"Sathvik Belagodu","family":"Sridhar","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dubai Medical University, Dubai P.O. Box 20170, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-5909","authenticated-orcid":false,"given":"Javedh","family":"Shareef","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical & Health Sciences University, Ras al Khaimah P.O. Box 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2500-9277","authenticated-orcid":false,"given":"Rakesh","family":"Sahu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sharda University, Knowledge Park III, Greater Noida 201310, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roja Rani","family":"Budha","sequence":"additional","affiliation":[{"name":"School of Pharmacy, D Y Patil Deemed to be University, Sector 7, Nerul, Navi Mumbai 400706, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-4512","authenticated-orcid":false,"given":"Mohd","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun 248002, Uttarakhand, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-0565","authenticated-orcid":false,"given":"Mohammad Amjad","family":"Kamal","sequence":"additional","affiliation":[{"name":"Future Technologies Research Centre, King Faisal University, P.O. Box 400, Al Ahsa 31982, Saudi Arabia"},{"name":"Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/his.13642","article-title":"Breast cancer intratumour heterogeneity: Current status and clinical implications","volume":"73","author":"Joseph","year":"2018","journal-title":"Histopathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.clbc.2020.03.004","article-title":"A Review of Breast Density Implications and Breast Cancer Screening","volume":"20","author":"Lian","year":"2020","journal-title":"Clin. 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