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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.
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.
In plain words · A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
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.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
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.
“HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test”
ENHERTU prescribing information; scoring bands from the ASCO/CAP 2018 guideline| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| IHC 3+ or ISH+ | Trastuzumab deruxtecan | HER2-positive breast cancer | FDA | label |
| IHC 3+ 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. | Trastuzumab deruxtecan | Metastatic cancer (cancer that has spread) | FDA | label |
| IHC 3+ or IHC 2+/ISH+ | Trastuzumab deruxtecan | HER2-positive gastric cancer | FDA | label |
| HER2 overexpression or amplification | Trastuzumab | HER2-positive breast cancer | FDA | label |
| HER2 overexpression (gastric scoring) | Trastuzumab | HER2-positive gastric cancer | FDA | label |
| IHC 3+ | Zanidatamab | Biliary tract cancer (all types) | FDA | label |
| IHC 3+ (with chemotherapy) or IHC 3+ or IHC 2+/ISH+ (with chemotherapy and tislelizumab) | Zanidatamab | HER2-positive gastric cancer | FDA | label |
| HER2-positive | Trastuzumab emtansine | HER2-positive breast cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| HercepTest | Dako Denmark A/S (Agilent) | Breast Cancer - Tissue | Trastuzumab | P980018 (09/25/1998) |
| HercepTest | Dako Denmark A/S (Agilent) | Gastric and Gastroesophageal Cancer - Tissue | Trastuzumab | P980018/S010 (10/20/2010) |
| PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody | Ventana Medical Systems (Roche) | Breast Cancer - Tissue | Trastuzumab | P990081 (11/28/2000) |
| PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody | Ventana Medical Systems (Roche) | Biliary Tract Cancer (gallbladder adenocarcinoma, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma) - Tissue | Zanidatamab | P990081/S054 (11/20/2024) |
| PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody | Ventana Medical Systems (Roche) | Breast Cancer - Tissue | Trastuzumab deruxtecanPertuzumab | P990081/S059 (12/15/2025) |
| Bond Oracle HER2 IHC System | Leica Biosystems | Breast Cancer - Tissue | Trastuzumab | P090015 (04/18/2012) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.
The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.
This is the paper Europe PMC returns for registry id NCT04744831 with the most citations, so it is the natural first reading for anyone following the DESTINY-CRC02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.
One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
The highest gallbladder HER2 rate in the literature comes from whole resected tumours scored generously; biopsy-based trial screening finds fewer. Heterogeneity is the practical warning for pathologists and for why HER2-directed drugs do not work in every positive tumour.
It fixes the population size for HER2-directed therapy, shows the enrichment in wild-type disease that makes reflex HER2 testing worthwhile there, and establishes that HER2 is not itself prognostic in this cancer.
It is the threshold behind the colorectal HER2 approvals: the more-than-50% rule, rather than the 10% used in gastric cancer, is what a pathologist applies when a bowel cancer is called HER2-positive.
Shares Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong), HER2-positive gastric cancer, Immunohistochemistry (IHC), Gallbladder cancer and the tag biomarker.
Shares Biliary tract cancer (all types), Gallbladder cancer, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.
Shares HER2 (ERBB2) activating mutation, HER2 and the tag biomarker.
Shares Immunohistochemistry (IHC), Gallbladder cancer, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.
Shares HER3 expression and the tag biomarker.
Shares Gallbladder cancer, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.
Shares HER2 (ERBB2) activating mutation and the tag biomarker.
Shares Gallbladder cancer, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.