{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:58:38Z","timestamp":1791295118409,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The clinical utility of the 21-gene recurrence score (RS) for guiding adjuvant chemotherapy in patients with pN2-3 early-stage breast cancer (eBC) has not been evaluated in prospective trials. This study aims to assess adjuvant chemotherapy benefit in patients with pN2-3 eBC who underwent RS testing and had a RS\u2009\u2264\u200925.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a retrospective cohort study from the National Cancer Database (NCDB) among patients with hormone receptor-positive\/HER2-negative, pN2-3 eBC diagnosed from 2010-2020 who underwent 21-gene RS testing (OncotypeDX) and had RS\u2009\u2264\u200925. Overall survival (OS) was compared between patients who received or did not receive chemotherapy, using propensity score (PS)-weighted Cox regression.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 50,229 eligible patients with pN2-3 eBC, 3,110 (6%) underwent RS testing. Patients who underwent testing had longer OS than those who did not (5-year OS: 86% vs. 79%). Among tested patients, 2,058 (66%) had RS\u2009\u2264\u200925 (median: 15), and 68% of them received chemotherapy. At a median follow-up of 5.3 years, the PS-weighted hazard ratio for OS comparing chemotherapy to no chemotherapy was 0.62 (95% CI: 0.48-0.81; P\u2009=\u20090.0002; E-value: 2.13, 95% CI lower bound: 1.58).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In this cohort of highly selected patients with hormone receptor-positive\/HER2-negative pN2-3 eBC who underwent 21-gene RS testing and had RS\u2009\u2264\u200925, patients who received chemotherapy had a longer OS compared to those who did not receive chemotherapy, despite having similar characteristics. These results should be interpreted with caution, as the presence of confounding by indication and residual confounding in this analysis underscores the need for randomized clinical trials in this population.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jnci\/djag374","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:32:22Z","timestamp":1791286342000},"source":"Crossref","is-referenced-by-count":0,"title":["21-Gene recurrence score assay in pN2-3 Early-Stage breast cancer: a national cancer database study"],"prefix":"10.1093","author":[{"given":"Carmine","family":"Valenza","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]},{"name":"European Institute of Oncology, IRCCS Division of New Drugs and Early Drug Development for Innovative Therapies, , Milan,","place":["Italy"]},{"name":"University of Milan Department of Oncology and Hemato-Oncology, , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zheng","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Division of Biostatistics, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Pablo","family":"Leone","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Trapani","sequence":"additional","affiliation":[{"name":"European Institute of Oncology, IRCCS Division of New Drugs and Early Drug Development for Innovative Therapies, , Milan,","place":["Italy"]},{"name":"University of Milan Department of Oncology and Hemato-Oncology, , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo Maria","family":"Berton Giachetti","sequence":"additional","affiliation":[{"name":"European Institute of Oncology, IRCCS Division of New Drugs and Early Drug Development for Innovative Therapies, , Milan,","place":["Italy"]},{"name":"University of Milan Department of Oncology and Hemato-Oncology, , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Nader-Marta","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S","family":"Dominici","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA,","place":["USA"]},{"name":"Beth Israel Deaconess Medical Center Division of Breast Surgery, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M","family":"Tolaney","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H","family":"Partridge","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"European Institute of Oncology, IRCCS Division of New Drugs and Early Drug Development for Innovative Therapies, , Milan,","place":["Italy"]},{"name":"University of Milan Department of Oncology and Hemato-Oncology, , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith M","family":"Regan","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA,","place":["USA"]},{"name":"Dana-Farber Cancer Institute Division of Biostatistics, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold J","family":"Burstein","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Medical Oncology, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,6]]},"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djag374\/71627104\/djag374.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djag374\/71627104\/djag374.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:14:29Z","timestamp":1791292469000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article\/doi\/10.1093\/jnci\/djag374\/8868973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/jnci\/djag374","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"djag374"}}