{"entity":{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","aka":["HER2 IHC 3+","HER2 3+","IHC 3+","HER2 overexpression","HER2-positive IHC","HER2 protein overexpression"],"tldr":"IHC 3+ means strong, complete membrane staining for HER2 in more than 10 percent of tumour cells. It is HER2-positive without needing a gene test and is the gate for trastuzumab, its combinations and antibody-drug conjugates in breast, stomach, biliary and, since 2024, any solid tumour.","summary":"Under the ASCO/CAP guideline an IHC score of 3+ is circumferential membrane staining that is complete, intense and in more than 10 percent of tumour cells; 3+ is HER2-positive on its own, 2+ is equivocal and goes to in situ hybridisation, 0 and 1+ are negative for trastuzumab purposes. Trastuzumab, pertuzumab, trastuzumab emtansine, tucatinib, margetuximab and neratinib are labelled for HER2-positive (overexpressing or amplified) breast cancer; trastuzumab is labelled for HER2-overexpressing gastric or GEJ adenocarcinoma, where the gastric scoring rules allow incomplete basolateral staining. Trastuzumab deruxtecan is labelled for HER2-positive (IHC 3+ or ISH+) breast cancer and, tumour-agnostically, for HER2-positive (IHC 3+) solid tumours after prior therapy, where the label notes no FDA-authorised test yet exists. Zanidatamab is labelled for HER2-positive (IHC 3+) biliary tract cancer and, with chemotherapy, IHC 3+ gastro-oesophageal adenocarcinoma.","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":"Herceptin prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2"},{"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-2-plus","her2-ihc-1-plus","her2-ihc-0","her2-low-ihc","her2-ultralow","her2-ish-amplified","her2-mutation"],"cancers":["breast-her2-positive","her2-positive-early-breast-cancer","gastric-her2-positive","biliary-tract-cancer","metastatic-cancer","colorectal","gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","pertuzumab","trastuzumab-emtansine","trastuzumab-deruxtecan","tucatinib","margetuximab","neratinib","zanidatamab","her2-testing-assays"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-positive","ihc","dual-her2-blockade","her2-testing-in-biliary-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016","paper-harding-lancet-oncol","paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","paper-hiraoka-her2-status-biliary-hum-pathol-2020","paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer: the colorectal-specific rule requires intense membranous staining in more than 50% of cells, against the 10% used in gastric cancer, because the colorectal-specific criteria were written and validated separately on 256 archival and 830 screening samples (Valtorta 2015). Overexpression was found in 2.2% of stage IV and 1.3% of stage II-III patients, and rose to 5.2% in KRAS and BRAF wild-type stage IV disease (Richman 2016).","Gallbladder and biliary cancer: HERIZON-BTC-01 confirmed ERBB2 amplification by central in situ hybridisation and treated IHC 2+ or 3+ as HER2-positive (Harding 2023); the zanidatamab label requires IHC 3+ with the Ventana PATHWAY 4B5 assay. Scoring follows the gastro-oesophageal guideline, which accepts incomplete basolateral staining. In 140 resected biliary cancers 6.4% were 3+, every 3+ tumour was amplified, and staining often involved under half of tumour cells (Angerilli 2026); heterogeneity was seen in 83% of HER2-positive biliary cancers, with loss in deeper invasive areas (Hiraoka 2020). In the DESTINY-PanTumor02 biliary cohort the objective response rate was 56.3% in centrally confirmed IHC 3+ tumours against 22.0% overall (Oh 2026)."],"target":"her2","measurement":"ihc-score","scoringRule":{"text":"3+: circumferential membrane staining that is complete, intense and in more than 10 percent of tumour cells. 2+: weak to moderate complete staining in more than 10 percent, or intense complete staining in 10 percent or less (equivocal, reflex to ISH). 1+: incomplete faint staining in more than 10 percent. 0: no staining or incomplete faint staining in 10 percent or less.","quote":"HER2-positive (IHC 3+ or 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 bands from the ASCO/CAP 2018 guideline"},"thresholds":[{"value":"IHC 3+ or ISH+","drugId":"trastuzumab-deruxtecan","cancerId":"breast-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"ENHERTU, in combination with pertuzumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test","status":"current"},{"value":"IHC 3+","drugId":"trastuzumab-deruxtecan","cancerId":"metastatic-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6","quote":"Select patients for treatment of unresectable or metastatic solid tumors with ENHERTU based on HER2-positive (IHC 3+) specimens","status":"current","note":"The label adds: An FDA-authorized test for the detection of HER2-positive (IHC 3+) solid tumors for treatment with ENHERTU is not currently available."},{"value":"IHC 3+ or IHC 2+/ISH+","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":"Select patients with locally advanced or metastatic HER2-positive gastric cancer based on HER2 protein overexpression or HER2 gene amplification (IHC 3+ or IHC 2+/ISH+).","status":"current"},{"value":"HER2 overexpression or amplification","drugId":"trastuzumab","cancerId":"breast-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2","quote":"Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens","status":"current"},{"value":"HER2 overexpression (gastric scoring)","drugId":"trastuzumab","cancerId":"gastric-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2","quote":"Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-authorized tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers.","status":"current"},{"value":"IHC 3+","drugId":"zanidatamab","cancerId":"biliary-tract-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae5d9425-fae5-4541-a158-150998343348","quote":"Select patients for treatment of unresectable or metastatic biliary tract cancer based on HER2-positive (IHC 3+) tumor specimens, as detected by an FDA-authorized test","status":"current"},{"value":"IHC 3+ (with chemotherapy) or IHC 3+ or IHC 2+/ISH+ (with chemotherapy and tislelizumab)","drugId":"zanidatamab","cancerId":"gastric-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae5d9425-fae5-4541-a158-150998343348","quote":"in combination with fluoropyrimidine- and platinum-containing chemotherapy, and tislelizumab-jsgr, as first-line treatment of adult patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test.","status":"current"},{"value":"HER2-positive","drugId":"trastuzumab-emtansine","cancerId":"breast-her2-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","quote":"Assessment of HER2 protein overexpression and/or HER2 gene amplification should be performed using FDA-authorized tests specific for breast cancers by laboratories with demonstrated proficiency.","status":"current"}],"tests":["caris-mi-profile"],"assays":["her2-herceptest","her2-pathway-4b5"],"companionDiagnostics":[{"device":"HercepTest","maker":"Dako Denmark A/S (Agilent)","companyId":"agilent","drugs":["trastuzumab"],"indication":"Breast Cancer - Tissue","pma":"P980018 (09/25/1998)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"HercepTest","maker":"Dako Denmark A/S (Agilent)","companyId":"agilent","drugs":["trastuzumab"],"indication":"Gastric and Gastroesophageal Cancer - Tissue","pma":"P980018/S010 (10/20/2010)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody","maker":"Ventana Medical Systems (Roche)","drugs":["trastuzumab"],"indication":"Breast Cancer - Tissue","pma":"P990081 (11/28/2000)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody","maker":"Ventana Medical Systems (Roche)","drugs":["zanidatamab"],"indication":"Biliary Tract Cancer (gallbladder adenocarcinoma, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma) - Tissue","pma":"P990081/S054 (11/20/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody","maker":"Ventana Medical Systems (Roche)","drugs":["trastuzumab-deruxtecan","pertuzumab"],"indication":"Breast Cancer - Tissue","pma":"P990081/S059 (12/15/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Bond Oracle HER2 IHC System","maker":"Leica Biosystems","drugs":["trastuzumab"],"indication":"Breast Cancer - Tissue","pma":"P090015 (04/18/2012)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A 3+ result means your cancer makes a lot of HER2 and is HER2-positive; no further gene test is needed. In breast and stomach cancer it opens trastuzumab-based treatment; since 2024 trastuzumab deruxtecan can be used for a 3+ tumour of almost any type once other treatments have been tried. A 2+ result is not an answer on its own and should be followed by an ISH test."},"route":"/biomarkers/her2-ihc-3-plus/","neighbours":{"biomarker":[{"id":"cldn18-2-expression","kind":"biomarker","name":"Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)","route":"/biomarkers/cldn18-2-expression/"},{"id":"her2-mutation","kind":"biomarker","name":"HER2 (ERBB2) activating mutation","route":"/biomarkers/her2-mutation/"},{"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-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/"},{"id":"her3-expression","kind":"biomarker","name":"HER3 expression","route":"/biomarkers/her3-expression/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"}],"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":"margetuximab","kind":"drug","name":"Margetuximab","route":"/drugs/margetuximab/"},{"id":"neratinib","kind":"drug","name":"Neratinib","route":"/drugs/neratinib/"},{"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/"},{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","route":"/drugs/trastuzumab-emtansine/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"},{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","route":"/drugs/zanidatamab/"}],"term":[{"id":"dual-her2-blockade","kind":"term","name":"Dual HER2 blockade","route":"/terms/dual-her2-blockade/"},{"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-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/"}],"paper":[{"id":"paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","kind":"paper","name":"Assessment of a HER2 scoring system for colorectal cancer: results from a validation study","route":"/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/"},{"id":"paper-hiraoka-her2-status-biliary-hum-pathol-2020","kind":"paper","name":"Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer","route":"/key-papers/paper-hiraoka-her2-status-biliary-hum-pathol-2020/"},{"id":"paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026","kind":"paper","name":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02","route":"/key-papers/paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026/"},{"id":"paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016","kind":"paper","name":"HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials","route":"/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/"},{"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-destiny-crc02-lancet-oncol-2024","kind":"paper","name":"Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial","route":"/key-papers/paper-destiny-crc02-lancet-oncol-2024/"},{"id":"paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)","route":"/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/"},{"id":"paper-harding-lancet-oncol","kind":"paper","name":"Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study","route":"/key-papers/paper-harding-lancet-oncol/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}]}}