{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:47:29Z","timestamp":1782298049879,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":174,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002336","name":"Daiichi Sankyo Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["T-DXd; DS-8201"],"award-info":[{"award-number":["T-DXd; DS-8201"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Breast Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Historically, HER2 status in invasive breast cancer has been categorized as HER2\u2010positive (IHC 3+, IHC 2+\/ISH+) or HER2\u2010negative (IHC 0, IHC 1+, IHC 2+\/ISH\u2010). Patients meeting IHC 0 with membrane staining (HER2\u2010ultralow) criteria may benefit from HER2\u2010targeted therapies such as trastuzumab deruxtecan. This cohort study assessed the prevalence of HER2\u2010ultralow expression by re\u2010scoring HER2 IHC slides using Mayo Clinic electronic health record data. Three hundred patients with advanced breast cancer (Stages III\u2010IV) and documented HER2 IHC 0 status (January 2017\u2013March 2023) were identified. One slide per patient was digitized and independently re\u2010scored by two Mayo Clinic pathologists following the 2023 ASCO\u2010CAP guidelines, including tumor staining percentage to denote HER2\u2010ultralow status. A sensitivity analysis was performed by a third independent pathologist. The re\u2010scored patients had a mean age of 57.7\u2009years (SD\u2009=\u200913.6). Most samples (95%,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009285) remained scored IHC 0 by at least one pathologist; 60% of these met HER2\u2010ultralow criteria per at least one pathologist. HER2\u2010ultralow prevalence ranged from 43% to 45% per pathologist, with 57% overall interpathologist concordance. Samples with no observable staining comprised most of the concordant cases. Treatment patterns were similar between HER2\u2010ultralow and no\u2010staining groups; however, time to treatment failure (TTF) varied between groups across lines of therapy (LOT). In HR\u2212 positive cohorts, median TTF for LOT1 was 7.73\u2009months in patients with HER2\u2010ultralow versus 9.43\u2009months with no observable IHC staining. In HR\u2212 negative cohorts, median TTF was 5.00\u2009months for HER2\u2010ultralow versus 3.17\u2009months with no observable IHC staining. Similar TTF trends were observed in LOT2\u2010LOT3. Approximately three in five samples originally classified as IHC 0 met HER2\u2010ultralow criteria, suggesting many patients may benefit from HER2\u2010directed therapy if reclassified. These findings highlight potential challenges of identifying HER2\u2010ultralow expression and suggest the need for enhanced pathologist training, adherence to best practices, and integration of digital pathology and artificial intelligence solutions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    ClinicalTrials.gov_identifier: NCT03734029\n                  <\/jats:p>","DOI":"10.1155\/tbj\/7212120","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:06:25Z","timestamp":1782295585000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HER2\u2010Ultralow: Prevalence, Characteristics, and Treatment Choices Among Advanced Breast Cancer Patients With Tumors Initially Scored as IHC 0"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3561-7818","authenticated-orcid":false,"given":"Anushree R.","family":"Iyengar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erinn P.","family":"Downs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6774-3927","authenticated-orcid":false,"given":"Nivedita","family":"Rangarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Sue-Ann","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone T.","family":"Sredni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie Di","family":"Donato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safak","family":"Simsek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren M.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Krieser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise Bieri","family":"Patzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Kyek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7347-8708","authenticated-orcid":false,"given":"Tyler","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Hipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6678-9329","authenticated-orcid":false,"given":"Aziza","family":"Nassar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4685-0680","authenticated-orcid":false,"given":"Hannah","family":"Barman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2203690"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2407086"},{"key":"e_1_2_13_3_2","article-title":"Prevalence of Low HER2 Expression Among HER2 Negative Metastatic Breast Cancer Patients in U.S: Multi-Site, Retrospective Chart Review Study","author":"Mehta S.","year":"2021","journal-title":"National Comprehensive Cancer Network Virtual Annual Conference"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2021.39.15_suppl.1021"},{"key":"e_1_2_13_5_2","article-title":"Patient Characteristics, Treatment Patterns, and Clinical Outcomes of Patients With Locally Advanced or Metastatic HER2-low Breast Cancer","author":"Watanabe A. 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SciBERT: A Pretrained Language Model for Scientific Text Proceedings of the 2019 Conference on Empirical Methods in Natural Language Processing and the 9th International Joint Conference on Natural Language Processing (EMNLP-IJCNLP) 2019 Hong Kong China Association for Computational Linguistics 3613\u20133618 https:\/\/www.aclweb.org\/anthology\/D19-1371.","DOI":"10.18653\/v1\/D19-1371"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/cci.23.00151"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.02864"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.2307\/2529310"},{"key":"e_1_2_13_12_2","unstructured":"National Comprehensive Cancer Network Inc. 2025. All Rights Reserved 2025 Referenced With Permission From the Nccn Clinical Practice Guidelines in Oncology (Nccn Guidelines) for Breast Cancer V.4"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2023.06.005"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2022.100009"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.2259"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-023-07079-8"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880440"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2022.100032"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/his.15275"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13010168"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36811-z"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2022.100054"}],"container-title":["The Breast Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbj\/7212120","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/tbj\/7212120","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbj\/7212120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:06:37Z","timestamp":1782295597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/tbj\/7212120"}},"subtitle":[],"editor":[{"given":"Hannah","family":"Wesley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/tbj\/7212120"],"URL":"https:\/\/doi.org\/10.1155\/tbj\/7212120","archive":["Portico"],"relation":{},"ISSN":["1075-122X","1524-4741"],"issn-type":[{"value":"1075-122X","type":"print"},{"value":"1524-4741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"7212120"}}