{"entity":{"id":"her2-positive","kind":"term","name":"HER2-positive (IHC 3+ or ISH-amplified)","aka":["HER2-positive","HER2 positive","HER2+","HER2-negative","HER2 negative","HER2−","IHC 3+","IHC 2+","HER2 IHC","HER2-amplified","HER2 amplification","ISH-amplified","HER2 overexpression","HER2-overexpressing","HER2-mutant","HER2 status","ASCO/CAP"],"tldr":"A cancer with too much HER2 growth-signal protein, either scored 3+ on the stain or shown to have extra copies of the gene. Once the most aggressive breast cancer subtype, it is now among the most treatable thanks to anti-HER2 drugs.","summary":"About 15-20% of breast cancers and a similar share of gastric/GEJ cancers are HER2-positive by ASCO/CAP criteria (IHC 3+, or IHC 2+ with in situ hybridisation amplification). They receive trastuzumab, pertuzumab, T-DM1 and T-DXd in curative and metastatic settings, with response-adapted pathways (KATHERINE, DESTINY-Breast). HER2-low (IHC 1+ or 2+/ISH-negative) and ultralow tumours are not 'positive' but respond to T-DXd, so the category is now a spectrum. HER2 mutations (rather than amplification) in lung cancer are targeted by T-DXd and zongertinib; HER2 amplification also occurs in colorectal, bladder and biliary cancers.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/HER2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HER2"},{"label":"Royal College of Pathologists G148: dataset for histopathological reporting of breast disease in surgical excision specimens of breast cancer, version 3, November 2024 (full review due November 2026)","url":"https://www.rcpath.org/resourceLibrary/g148-dataset-for-histopathological-reporting-of-breast-disease-in-surgical-excision-specimens-of-breast-cancer.html"},{"label":"Rakha et al., Journal of Clinical Pathology 2023;76:217 to 227: UK recommendations for HER2 assessment in breast cancer, an update","url":"https://doi.org/10.1136/jcp-2022-208632"}],"tags":[],"related":["her2-low","fish","hormone-receptor-status","ihc","her2-testing-uk-breast"],"cancers":["breast-her2-positive","gastric","nsclc"],"sections":["targeted-therapy","diagnostics"],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","trastuzumab-deruxtecan","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-testing-uk-breast","receptor-conversion-breast"],"trials":["katherine","aphinity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Britain and America classify one borderline group differently. Cases with a HER2 to chromosome 17 ratio of 2.0 or more but a HER2 copy number below 4 (ASCO and CAP's FISH group 2) are negative under the American guideline and positive under the UK recommendations, which the RCPath dataset in force restates and declines to change. The UK also asks for dual-probe in situ hybridisation with the ratio, the HER2 copy number and the chromosome 17 copy number all reported, and puts HER2 positivity at 13 to 20 percent of early breast cancer."],"category":"Biomarkers"},"route":"/terms/her2-positive/","neighbours":{"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","route":"/terms/gene-amplification/"},{"id":"grade-stage-receptor-breast","kind":"term","name":"Grade, stage and receptor status: three different things on one breast report","route":"/terms/grade-stage-receptor-breast/"},{"id":"her2-testing-in-biliary-cancer","kind":"term","name":"HER2 testing in biliary tract cancer (IHC, ISH and NGS)","route":"/terms/her2-testing-in-biliary-cancer/"},{"id":"her2-testing-uk-breast","kind":"term","name":"HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP","route":"/terms/her2-testing-uk-breast/"},{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/"},{"id":"hormone-receptor-status","kind":"term","name":"Hormone receptor status (ER / PR)","route":"/terms/hormone-receptor-status/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"receptor-conversion-breast","kind":"term","name":"Receptor conversion: when the receptors change between the primary and a recurrence","route":"/terms/receptor-conversion-breast/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","route":"/drugs/her2-testing-assays/"},{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"trial":[{"id":"aphinity","kind":"trial","name":"APHINITY","route":"/trials/aphinity/"},{"id":"katherine","kind":"trial","name":"KATHERINE","route":"/trials/katherine/"}],"paper":[{"id":"paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","kind":"paper","name":"HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases","route":"/key-papers/paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026/"},{"id":"paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017","kind":"paper","name":"HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?","route":"/key-papers/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017/"},{"id":"paper-toga-trastuzumab-gastric-lancet-2010","kind":"paper","name":"ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer","route":"/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/"}],"roadmap":[{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"}],"idea":[{"id":"idea-gbc-reflex-her2-testing-advanced-biliary","kind":"idea","name":"Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer","route":"/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/"}],"biomarker":[{"id":"her2-ihc-2-plus","kind":"biomarker","name":"HER2 IHC 2+ (equivocal, reflex to ISH)","route":"/biomarkers/her2-ihc-2-plus/"},{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 ISH amplified (ERBB2 gene amplification)","route":"/biomarkers/her2-ish-amplified/"}]}}