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This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted up to October 2025 to identify studies evaluating Trop-2 protein expression levels and clinical outcomes in patients with BC receiving Trop-2\u2013directed antibody-drug conjugates (ADCs) or chemotherapy. Random-effects meta-analyses were performed to estimate pooled Trop-2 positivity rates and to assess progression-free (PFS) and overall survival (OS) across Trop-2 expression levels. Additionally, an association analysis between Trop-2 protein and gene expression was performed in an early BC patient cohort (n\u2009=\u2009564) using immunohistochemistry and gene expression data. Trop-2 protein expression was assessed using both conventional observer-based methods and digital quantitative image analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 41 studies fulfilled the inclusion criteria. The overall pooled Trop-2 protein positivity rate was 72% [95% Confidence Interval (CI), 67\u201377%; 41 studies, n\u2009=\u20099170]. Trop-2\u2013directed ADCs improved PFS versus chemotherapy across different H-score groups, with the greatest benefit in tumours with high H-score [3 studies; n\u2009=\u2009575; Hazard Ratio (HR)\u2009=\u20090.33, 95% CI 0.20\u20130.56, p\u2009&lt;\u20090.0001]. For OS, the benefit was observed in the low H-score group (2 studies; n\u2009=\u2009272; HR\u2009=\u20090.75, 95% CI 0.57\u20130.98, p\u2009=\u20090.034). In the study cohort, Trop-2 protein by observer-read assessment was detected in 396\/454 patients (87.22%). Digital pathology identified 54 (11.90%) tumours with low, 326 (71.80%) with medium, and 74 (16.30%) with high H-scores. Observer-read and digital assessments were significantly associated (Pearson\u2019s chi-square test, p\u2009&lt;\u20090.001). Higher Trop-2 protein and gene expression were associated with worse distant recurrence-free interval (HR\n                      <jats:sub>adj<\/jats:sub>\n                      \u2009=\u20091.45, 95%\u2009CI 1.01\u20132.08, p\u2009=\u20090.04 and HR\n                      <jats:sub>adj<\/jats:sub>\n                      \u2009=\u20091.33, 95%\u2009CI 1.05\u20131.68, p\u2009=\u20090.02, respectively), particularly in Luminal B subtype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Trop-2 was detectable across all BC subtypes, exhibiting a wide range of expression levels. Our study suggests that Trop-2 may have a potential prognostic significance in early BC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-026-05093-3","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:34:25Z","timestamp":1785465265000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Trophoblast cell surface antigen 2 (Trop-2) expression and its clinical significance in breast cancer: a multi-level analysis of protein and gene expression"],"prefix":"10.1186","volume":"24","author":[{"given":"Maria Angeliki","family":"Toli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Sarafidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Filis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Tzoras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Tsiknakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil","family":"Sifakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathia","family":"Liatsou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Rassidakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Bergh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexios","family":"Matikas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Zerdes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Foukakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"8","key":"5093_CR1","doi-asserted-by":"publisher","first-page":"5147","DOI":"10.1073\/pnas.78.8.5147","volume":"78","author":"M Lipinski","year":"1981","unstructured":"Lipinski M, Parks DR, Rouse RV, Herzenberg LA. 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No additional written informed consent was needed for each patient included in the study.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Jonas Bergh: Research funding to institution (Karolinska Institutet and\/or Karolinska University Hospital from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi (no personal honoraria); honoraria as co-author for breast cancer chapters from UpToDate paid to Asklepios Medicin HB; head of advisory board at Stratipath AB; Coronis and Asklepios Cancer Research AB hold shares of Stratipath AB; honoraria for lectures\/educational conferences for postgraduate courses from AstraZeneca paid to Coronis and Asklepios Cancer Research AB, chairmanship for meetings arranged by Akademikonferens, on behalf of Roche, and lectures for Novartis and Gilead, respectively; honoraria to Coronis and Asklepios Cancer Research AB, for both activities. Ioannis Zerdes: Institutional research grants from Gilead; honoraria from Novartis (institutional) and BioMed Central Ltd (part of Springer Nature) (personal). Alexios Matikas: Speaker (no personal payment): Seagen, Roche, AstraZeneca; Expert testimony (no financial or non-financial compensation): Veracyte, Roche, AstraZeneca; Research funding (paid to institution): MSD, Novartis, Veracyte, AstraZeneca; Advisory Board (no financial or non-financial compensation): Nordic Pharma. Theodoros Foukakis: Invited Speaker, Payment to Institution: Roche, Astra Zeneca, Gilead Sciences, Novartis, Daiichi Sankyo, Bristol Myers Squibb; royalties, personal: Wolters Kluwer (authorship of two chapters in UpToDate); clinical trial support to Institution: Astra Zeneca, Coordinating PI (research grant and study drug), Novartis, Coordinating PI (research grant and study drug), Veracyte, Coordinating PI (discount on the ProsignaPAM50 assay in ARIADNE clinical trial). The remaining authors declare that they have no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"422"}}