{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:03:44Z","timestamp":1784282624363,"version":"3.55.0"},"reference-count":36,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2026,5,16]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare changes in HER2 expression status on reassessment across multiple clinical groups using new three-tier versus traditional binary HER2 reporting schemas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective study of 1107 paired IBC samples wherein HER2 immunohistochemistry (IHC) and, where needed, in-situ hybridisation (ISH) were performed at least twice in four clinical groups: core needle biopsy (CNB)-upfront resection (n=277); CNB-post-chemotherapy resection (n=104); primary (CNB\/resection)-recurrence (local\/metastatic, n=702); initial and subsequent distant metastasis (n=24). Concordance was noted for HER2-positive (HER2-IHC 3+ or 2+ ISH-amplified), negative (HER2-IHC 0) and low (HER2-IHC 1+ and 2+ ISH-non-amplified) status, and compared with the concordance of binary HER2 status (positive\/negative).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HER2 concordance dropped sharply to 69.7% (k=0.53, 95% CI 0.48 to 0.57) on reassessment after applying the three-tier schema, driven primarily by bidirectional shifts between HER2-negative (IHC 0) and HER2-low. Referral specimens showed poorer concordance than in-house tissue in both binary (p value &lt;0.001, OR: 2.40, 95%\u2009CI 1.40 to 4.10) and ternary classification (p value &lt;0.001, OR: 1.72, 95%\u2009CI 1.31 to 2.2), emphasising the effects of pre-analytical factors like fixation on HER2 interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The three-tier HER2-low classification schema demonstrates poor reproducibility on re-evaluation, with nearly one-third of cases discordant. This fluidity has significant therapeutic implications. We recommend HER2 re-evaluation with careful attention to the 0 versus 1+ distinction, especially in metastatic and post-treatment settings and when pre-analytical factors are suboptimal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2026-210710","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:20:17Z","timestamp":1779816017000},"page":"526-533","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Concordance of conventional two-tier HER2 classification versus three-tier classification (including HER2-low status) in invasive breast carcinoma: a retrospective real-world analysis"],"prefix":"10.1136","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4254-7370","authenticated-orcid":false,"given":"Archita","family":"Juneja","sequence":"first","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3574-8855","authenticated-orcid":false,"given":"Ayushi","family":"Sahay","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6904-8981","authenticated-orcid":false,"given":"Pooja","family":"Padwale","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asawari","family":"Patil","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trupti","family":"Pai","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Panjwani","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalaka","family":"Joshi","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabassum","family":"Wadasadawala","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palak","family":"Popat","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Radiology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanuja M","family":"Shet","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Gupta","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta B","family":"Desai","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"2026071702101077000_79.8.526.1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02864"},{"key":"2026071702101077000_79.8.526.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.05.008"},{"key":"2026071702101077000_79.8.526.3","unstructured":"College of American Pathologists . 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