{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:38Z","timestamp":1792785998687,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Recovery and Resilience Plan"},{"name":"Italian Ministry of University and Research"},{"name":"European Union\u2014NextGenerationEU\u2013Project","id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Elucidating its Functional Role and Clinical Significance in Estrogen Receptor-positive Breast Cancer\u2014CUP","award":["E53D23012930006"],"award-info":[{"award-number":["E53D23012930006"]}]},{"name":"Italian Ministry of University and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Trophoblast cell surface antigen 2 (Trop-2) is expressed across multiple tumors, including breast cancer. Antibody\u2013drug conjugates (ADCs) targeting Trop-2 have demonstrated efficacy in metastatic breast cancer. However, the extent to which clinical benefit varies according to Trop-2 expression remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta-analysis (PROSPERO: CRD420251074955) of phase II-III trials (conducted from January 2015 to September 2025), enrolling patients with metastatic breast cancer treated with Trop-2\u2013targeting ADCs, to assess the relationship between Trop-2 expression and treatment efficacy. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) were extracted according to study-defined Trop-2 levels. Pooled hazard ratios were estimated using fixed- or random-effects models based on heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five randomized trials (ASCENT, TROPiCS-02, EVER-132-002, OptiTROP-Breast01, and TROPION-Breast01), including 1879 patients treated with ADCs targeting Trop-2 or chemotherapy, were included. Trop-2\u2013targeted ADCs significantly improved PFS compared with chemotherapy in Trop-2\u2013high (HR = 0.34, 95% CI = 0.20 to 0.57) and Trop-2\u2013low (HR = 0.63, 95% CI = 0.50 to 0.79) subgroups in the overall metastatic breast cancer population and in triple-negative breast cancer (Trop-2\u2013high: HR = 0.27, 95% CI = 0.20 to 0.37; P\u2009&amp;lt;\u2009.001; Trop-2\u2013low: HR = 0.46, 95% CI = 0.33 to 0.64; P\u2009&amp;lt;\u2009.001). However, in hormone receptor\u2013positive\/HER2-negative metastatic breast cancer, a significant PFS benefit was observed only in the Trop-2\u2013high subgroup (HR = 0.56, 95% CI = 0.47 to 0.68; P\u2009&amp;lt;\u2009.001). Across all disease subtypes, the magnitude of PFS benefit was greater in Trop-2\u2013high tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ADCs targeting Trop-2 significantly improved PFS in metastatic breast cancer, but the therapeutic benefit was greater in those with high Trop-2 expression. These findings underscore the importance of standardized, clinically meaningful Trop-2 testing to optimize patient selection and treatment decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag220","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:53:17Z","timestamp":1783597997000},"source":"Crossref","is-referenced-by-count":1,"title":["Impact of Trop-2 expression on the efficacy of Trop-2\u2013targeted antibody\u2013drug conjugates in metastatic breast cancer: a systematic review and meta-analysis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-3224","authenticated-orcid":false,"given":"Roberto","family":"Buonaiuto","sequence":"first","affiliation":[{"name":"Department of Breast and Thoracic Oncology, Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d , Napoli,","place":["Italy"]},{"name":"Clinical and Translational Oncology, Scuola Superiore Meridionale , Naples,","place":["Italy"]},{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8114-2577","authenticated-orcid":false,"given":"Martina","family":"Pagliuca","sequence":"additional","affiliation":[{"name":"Clinical and Translational Oncology, Scuola Superiore Meridionale , Naples,","place":["Italy"]},{"name":"Universit\u00e9 Paris-Saclay, UVSQ, Gustave Roussy, Inserm, CESP, F-94800, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Longobardi","sequence":"additional","affiliation":[{"name":"Oncology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II , Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3396-8630","authenticated-orcid":false,"given":"Maria Letizia","family":"Cataldo","sequence":"additional","affiliation":[{"name":"Clinical and Translational Oncology, Scuola Superiore Meridionale , Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-0364","authenticated-orcid":false,"given":"Luca","family":"Arecco","sequence":"additional","affiliation":[{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7297-052X","authenticated-orcid":false,"given":"Riccardo","family":"Gerosa","sequence":"additional","affiliation":[{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]},{"name":"Department of Biomedical Sciences, Humanitas University , Pieve Emanuele, Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2714-2769","authenticated-orcid":false,"given":"Gabriella","family":"Gentile","sequence":"additional","affiliation":[{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]},{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza-University of Rome, Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-4333","authenticated-orcid":false,"given":"Aldo","family":"Caltavituro","sequence":"additional","affiliation":[{"name":"Clinical and Translational Oncology, Scuola Superiore Meridionale , Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Barone","sequence":"additional","affiliation":[{"name":"Centro Sanitario, University of Calabria , Arcavacata di Rende, CS,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6299-7844","authenticated-orcid":false,"given":"Bengisu","family":"Karakose","sequence":"additional","affiliation":[{"name":"Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, H\u00f4pital Universitaire de Bruxelles , Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-7511","authenticated-orcid":false,"given":"Elisa","family":"Agostinetto","sequence":"additional","affiliation":[{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Sotiriou","sequence":"additional","affiliation":[{"name":"Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, H\u00f4pital Universitaire de Bruxelles , Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelino","family":"De Laurentiis","sequence":"additional","affiliation":[{"name":"Department of Breast and Thoracic Oncology, Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d , Napoli,","place":["Italy"]},{"name":"Clinical and Translational Oncology, Scuola Superiore Meridionale , Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9501-4509","authenticated-orcid":false,"given":"Evandro","family":"De Azambuja","sequence":"additional","affiliation":[{"name":"Institut Jules Bordet, Universit\u00e9 libre de Bruxelles (ULB), H\u00f4pital Universitaire de Bruxelles (H.U.B) , Bruxelles,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-4630","authenticated-orcid":false,"given":"Carmine","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Breast and Thoracic Oncology, Istituto Nazionale Tumori IRCCS \u201cFondazione G. 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