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Variables were TTL (CK19 mRNA copies\/\u00b5L) in SLNs, number of LNs removed, and number of metastatic ones. We constructed receiver operating characteristics (ROC) curves to determine optimal TTL values and multivariate logistic regression models to identify relevant prognostic factors for predicting\u2009\u2265\u20094 LN metastases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 3804 patients with HR\u2009+\u2009\/HER2- tumors of any histological type, complete axillary LN dissection, and\u2009&gt;\u20094 LNs removed; 608 (16.0%) had\u2009\u2265\u20094 metastatic LNs and 439 had lobular BC. At cut-offs of 99,500 and 101,000 copies\/\u00b5L, TTL had a 32.3% and 32.4% PPV. In lobular BC, cut-offs between 92,305 and 108,700 copies\/\u00b5L reached a 40% PPV. In lobular HR\u2009+\u2009\/HER2- BC, a multivariate model including tumor grade, TTL, and lymphovascular invasion reached a 49% PPV for predicting\u2009\u2265\u20094 metastatic LNs, yielding a nomogram and an online calculator for use in routine practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TTL measured using OSNA predicts\u2009\u2265\u20094 metastatic LNs in patients with luminal-like BC, with a proposed optimal threshold of 100,000 copies\/\u00b5L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12094-026-04426-1","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T05:35:01Z","timestamp":1780724101000},"page":"5231-5239","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating total tumor load (TTL) to predict metastasis in four or more axillary lymph nodes in HR\u2009+\/HER2- breast cancer patients: the TULIP4N\u2009+\u2009study"],"prefix":"10.1007","volume":"28","author":[{"given":"Esther","family":"Zamora","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pi\u00f1ero-Madrona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Sperduti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sapino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Fougo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-6166","authenticated-orcid":false,"given":"Vicente","family":"Peg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"4426_CR1","doi-asserted-by":"publisher","first-page":"412","DOI":"10.5306\/wjco.v5.i3.412","volume":"5","author":"O Yersal","year":"2014","unstructured":"Yersal O, Barutca S. 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Patients provided their informed consent to participate in the six previous studies included in this pooled analysis.","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}}]}}