{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:56:07Z","timestamp":1793314567871,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"University of Padova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Even with contemporary treatment strategies, more than 10% of HER2-positive early stage breast cancer patients may experience distant metastasis as first event during follow-up. Tools for predicting unique patterns of metastatic spread are needed to plan personalized surveillance. We evaluated how molecular heterogeneity affects the pattern of distant relapse in HER2-positive breast cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 677 HER2-positive stage I-III breast cancer patients from ShortHER trial, Cher-LOB trial, and 2 institutional cohorts were included. PAM50 molecular subtypes and research-based HER2DX scores were evaluated. The cumulative incidence of distant relapse as the first event (any site and site specific) was evaluated using competing risk analysis. Median follow-up was 8.4\u2009years. Tests of statistical significance are 2-sided.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Stage III and high HER2DX risk score identified patients at the highest risk of distant relapse as first event (10-year incidence 24.5% and 19.7%, respectively). Intrinsic molecular subtypes were associated with specific patterns of metastatic spread: compared with other subtypes, HER2-enriched tumors were more prone to develop brain metastases (10-year incidence 3.8% vs 0.6%, P\u2009=\u2009.005), basal-like tumors were associated with an increased risk of lung metastases (10-year incidence 11.1% vs 2.6%, P\u2009=\u2009.001), and luminal tumors developed more frequently bone-only metastases (10-year incidence 5.1% vs 2.0%, P\u2009=\u2009.042). When added to stage or HER2DX risk score in competing risk regression models, intrinsic subtype maintained an independent association with site-specific metastases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The integration of intrinsic molecular subtypes with stage or HER2DX risk score predicts site-specific metastatic risk in HER2-positive breast cancer, with potential implications for personalized surveillance and clinical trials aimed at preventing site-specific recurrence.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djad179","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T17:01:39Z","timestamp":1694106099000},"page":"69-80","source":"Crossref","is-referenced-by-count":16,"title":["Metastatic site patterns by intrinsic subtype and HER2DX in early HER2-positive breast cancer"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3967-9861","authenticated-orcid":false,"given":"Maria Vittoria","family":"Dieci","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova , Padova, Italy"},{"name":"Oncology 2, Veneto Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) , Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-5344","authenticated-orcid":false,"given":"PierFranco","family":"Conte","sequence":"additional","affiliation":[{"name":"Veneto Oncology Network , Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-3771","authenticated-orcid":false,"given":"Giancarlo","family":"Bisagni","sequence":"additional","affiliation":[{"name":"Department of Oncology and Advanced Technologies, Oncology Unit, Azienda Unit\u00e0 Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) , Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-0109","authenticated-orcid":false,"given":"Stefania","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna , Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3487-3259","authenticated-orcid":false,"given":"Antonio","family":"Frassoldati","sequence":"additional","affiliation":[{"name":"Clinical Oncology, Department of Translational Medicine and for Romagna, S. 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