{"entity":{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","aka":[],"tldr":"The tests that grade a breast or stomach cancer's HER2 level, from the original trastuzumab test in 1998 to the new 'HER2-low' and 'ultralow' cut-offs.","summary":"HercepTest (Dako, PMA P980018, 25 September 1998) was the first companion diagnostic ever approved, launched with trastuzumab. Roche's PATHWAY anti-HER2/neu (4B5) and INFORM HER2 Dual ISH are the other FDA-approved workhorses, extended to gastric cancer with the ToGA trial. The HER2-low era changed what a score means: in October 2022 the FDA approved PATHWAY 4B5 as the companion diagnostic for trastuzumab deruxtecan in HER2-low (IHC 1+ or 2+/ISH-negative) metastatic breast cancer after DESTINY-Breast04, and in January 2025 extended it to HER2-ultralow (IHC 0 with membrane staining) after DESTINY-Breast06. A score of 0 versus 1+ that once meant nothing now decides eligibility for an antibody-drug conjugate, which has forced pathologists to re-standardise the low end of the scale.","status":"approved","asOf":"2026-09-10","links":[{"label":"FDA PMA P980018","url":"https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P980018"},{"label":"ASCO/CAP HER2 testing guideline update (2023)","url":"https://doi.org/10.1200/JCO.22.02864"}],"tags":["test"],"related":[],"cancers":["breast-her2-positive","breast-hr-positive","gastric","tnbc"],"sections":[],"technologies":["companion-diagnostic","histopathology-ihc","cytogenetics-fish"],"targets":["her2"],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":["agilent","roche-genentech"],"institutions":[],"pathways":[],"terms":["her2-positive","her2-low","ihc","fish"],"trials":["destiny-breast04","destiny-breast06"],"people":[],"bottlenecks":[],"keyPapers":["paper-schettini-her2-low-features-npj-breast-cancer-2021","paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","paper-wolff-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":["What a result means: 3+ (or 2+ with amplification) is HER2-positive and unlocks trastuzumab-based therapy; 1+ or 2+ without amplification is HER2-low and, in metastatic disease, unlocks trastuzumab deruxtecan."],"brand":"HercepTest / PATHWAY anti-HER2 (4B5) / INFORM HER2 Dual ISH","modality":"HER2 immunohistochemistry and in situ hybridisation companion diagnostic assays","mechanism":"Immunohistochemistry for HER2 protein scored 0, 1+, 2+ or 3+ under ASCO/CAP guidelines, with in situ hybridisation (FISH or dual-colour chromogenic ISH) to resolve 2+ cases by measuring ERBB2 gene amplification.","approvals":[{"region":"US","year":1998,"indication":"HercepTest: HER2 overexpression to select trastuzumab in breast cancer (first companion diagnostic)"},{"region":"US","year":2010,"indication":"HER2 testing extended to gastric and GEJ adenocarcinoma with trastuzumab (ToGA)"},{"region":"US","year":2022,"indication":"PATHWAY 4B5 as companion diagnostic for trastuzumab deruxtecan in HER2-low breast cancer"},{"region":"US","year":2025,"indication":"PATHWAY 4B5 extended to HER2-ultralow (IHC 0 with membrane staining)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/her2-testing-assays/","neighbours":{"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":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"agilent","kind":"company","name":"Agilent Technologies (Dako)","route":"/companies/agilent/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"genomic-testing-biliary-uk","kind":"term","name":"HER2 and genomic testing for biliary cancer on the NHS","route":"/terms/genomic-testing-biliary-uk/"},{"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-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/"},{"id":"her2-positive","kind":"term","name":"HER2-positive (IHC 3+ or ISH-amplified)","route":"/terms/her2-positive/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"trial":[{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"},{"id":"destiny-breast06","kind":"trial","name":"DESTINY-Breast06","route":"/trials/destiny-breast06/"}],"paper":[{"id":"paper-schettini-her2-low-features-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","route":"/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/"},{"id":"paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","kind":"paper","name":"Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status","route":"/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/"},{"id":"paper-wolff-j-clin-oncol","kind":"paper","name":"Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update","route":"/key-papers/paper-wolff-j-clin-oncol/"}],"biomarker":[{"id":"her2-ihc-0","kind":"biomarker","name":"HER2 IHC 0 (HER2-negative, including ultralow)","route":"/biomarkers/her2-ihc-0/"},{"id":"her2-ihc-1-plus","kind":"biomarker","name":"HER2 IHC 1+","route":"/biomarkers/her2-ihc-1-plus/"},{"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/"},{"id":"her2-low-ihc","kind":"biomarker","name":"HER2-low (IHC 1+ or IHC 2+/ISH-negative)","route":"/biomarkers/her2-low-ihc/"},{"id":"her2-ultralow","kind":"biomarker","name":"HER2-ultralow (IHC 0 with membrane staining)","route":"/biomarkers/her2-ultralow/"}],"roadmap":[{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-roadmap/"}]}}