HER2 IHC 3+ (HER2-positive by immunohistochemistry)

aka HER2 IHC 3+, HER2 3+, IHC 3+, HER2 overexpression, HER2-positive IHC, HER2 protein overexpression

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.

Part ofHER2· ERBB2Other readoutsHER2 HER2 IHC 0 HER2 IHC 1+HER2 IHC 2+HER2 ISH amplified HER2-low HER2-ultralow All readouts

HER2: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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.

IHC score 8 approval thresholds

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

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

Drugs whose label names it

Trastuzumab deruxtecan Trastuzumab Zanidatamab Trastuzumab emtansine

Companion diagnostics (FDA list)

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 deruxtecan Pertuzumab	P990081/S059 (12/15/2025)
Bond Oracle HER2 IHC System	Leica Biosystems	Breast Cancer - Tissue	Trastuzumab	P090015 (04/18/2012)

Tests that measure it

HercepTest PATHWAY anti-HER2/neu (4B5)Caris MI Profile

Trials that name this readout

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.