HER2 IHC 0 (HER2-negative, including ultralow)

aka HER2 IHC 0, HER2 0, IHC 0, HER2-negative IHC, HER2 null, IHC 0 with membrane staining

IHC 0 is no HER2 staining, or faint staining in 10 percent or fewer cells. It is HER2-negative, but the label now separates true zero from 'IHC 0 with membrane staining', the ultralow group that trastuzumab deruxtecan can treat in hormone-receptor-positive breast cancer.

The ASCO/CAP 0 band covers no staining and incomplete faint staining in 10 percent or fewer of tumour cells; the guideline treats it as a single negative category. DESTINY-Breast06 split it: tumours with any faint, incomplete membrane staining in 10 percent or fewer cells ('HER2-ultralow') responded to trastuzumab deruxtecan like HER2-low tumours, and the US label was expanded in January 2025 to HER2-low or HER2-ultralow (IHC 0 with membrane staining) HR-positive breast cancer after endocrine therapy. A true 0 with no staining at all remains outside every HER2-directed label. Distinguishing 0 from ultralow at the low end of the scale is the hardest read in HER2 pathology and the reason AI-assisted scoring is being validated.

Part ofHER2· ERBB2Other readoutsHER2 HER2 IHC 1+HER2 IHC 2+HER2 IHC 3+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 1 approval threshold

What it means for a patient

A 0 result means HER2-directed antibodies such as trastuzumab are not used. If your breast cancer is hormone-receptor-positive, ask whether the 0 was a true zero or 'with membrane staining' (ultralow), because the ultralow group can now receive trastuzumab deruxtecan once hormone therapy has stopped working.

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

0: no staining, or incomplete faint membrane staining in 10 percent or fewer of tumour cells. 'IHC 0 with membrane staining' (ultralow) is the sub-band with faint incomplete staining in 10 percent or fewer cells.

“HER2-ultralow (IHC 0 with membrane staining) breast cancer”
ENHERTU prescribing information; scoring band from the ASCO/CAP 2018 guideline

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
IHC 0 with membrane staining (ultralow), HR-positive	Trastuzumab deruxtecan	HER2-low and HER2-ultralow metastatic breast cancer	FDA	label

Drugs whose label names it

Trastuzumab deruxtecan

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
PATHWAY anti-Her2/neu (4B5) Rabbit Monoclonal Primary Antibody	Ventana Medical Systems (Roche)	Breast Cancer - Tissue	Trastuzumab deruxtecan	P990081/S055 (01/27/2025)

Tests that measure it

HercepTest PATHWAY anti-HER2/neu (4B5)

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.