{"entity":{"id":"her2-ihc-2-plus","kind":"biomarker","name":"HER2 IHC 2+ (equivocal, reflex to ISH)","aka":["HER2 IHC 2+","HER2 2+","IHC 2+","HER2 equivocal","2+/ISH","IHC 2+/ISH-negative","IHC 2+/ISH+"],"tldr":"IHC 2+ is the in-between HER2 result: moderate staining that cannot be called positive or negative by eye, so the laboratory runs an ISH gene test. 2+ with amplification is HER2-positive; 2+ without it is HER2-low.","summary":"A 2+ score is weak to moderate complete membrane staining in more than 10 percent of tumour cells (or intense complete staining in 10 percent or fewer) and is equivocal under ASCO/CAP; reflex in situ hybridisation decides. The result matters twice over: IHC 2+/ISH+ counts as HER2-positive for trastuzumab, pertuzumab, trastuzumab emtansine and trastuzumab deruxtecan, while IHC 2+/ISH- is one of the two HER2-low categories for trastuzumab deruxtecan after chemotherapy (DESTINY-Breast04) or after endocrine therapy (DESTINY-Breast06). In gastric cancer the trastuzumab label defines positivity as IHC 3+ or IHC 2+ with a positive ISH.","asOf":"2026-09-23","links":[{"label":"ENHERTU prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6"},{"label":"ASCO/CAP HER2 testing in breast cancer guideline, 2018 focused update (Wolff et al., J Clin Oncol)","url":"https://doi.org/10.1200/JCO.2018.77.8738"}],"tags":["biomarker","her2"],"related":["her2-ihc-3-plus","her2-ish-amplified","her2-low-ihc"],"cancers":["breast-cancer","her2-low-metastatic-breast-cancer","gastric-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","trastuzumab","her2-testing-assays"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-positive","her2-low","fish","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"her2","measurement":"ihc-score","scoringRule":{"text":"2+: weak to moderate complete membrane staining in more than 10 percent of tumour cells, or intense complete staining in 10 percent or fewer; classified equivocal and reflexed to in situ hybridisation.","quote":"HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","sourceLabel":"ENHERTU prescribing information; scoring band from the ASCO/CAP 2018 guideline"},"thresholds":[{"value":"IHC 2+/ISH+ (HER2-positive)","drugId":"trastuzumab-deruxtecan","cancerId":"gastric-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"based on HER2 protein overexpression or HER2 gene amplification (IHC 3+ or IHC 2+/ISH+)","status":"current"},{"value":"IHC 2+/ISH- (HER2-low)","drugId":"trastuzumab-deruxtecan","cancerId":"her2-low-metastatic-breast-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy","status":"current"}],"tests":[],"assays":["her2-herceptest","her2-pathway-4b5","her2-ish"],"companionDiagnostics":[{"device":"PATHWAY anti-Her2/neu (4B5) Rabbit Monoclonal Primary Antibody","maker":"Ventana Medical Systems (Roche)","drugs":["trastuzumab-deruxtecan"],"indication":"Breast Cancer - Tissue","pma":"P990081/S047 (09/30/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A 2+ result is not final. Your pathologist should run an ISH gene test on the same sample: if the HER2 gene is amplified the cancer is HER2-positive and trastuzumab-based treatment applies; if it is not, the cancer is HER2-low, which in breast cancer opens trastuzumab deruxtecan after earlier treatment."},"route":"/biomarkers/her2-ihc-2-plus/","neighbours":{"biomarker":[{"id":"her2-ihc-1-plus","kind":"biomarker","name":"HER2 IHC 1+","route":"/biomarkers/her2-ihc-1-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/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"}],"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":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"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/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}]}}