HER2-ultralow (IHC 0 with membrane staining)

aka HER2-ultralow, HER2 ultralow, ultralow, IHC 0 with faint staining, IHC >0 <1+

HER2-ultralow is an IHC 0 result with a trace of membrane staining in a few cells. Since 2025, in hormone-receptor-positive breast cancer that has stopped responding to hormone therapy, it is enough for trastuzumab deruxtecan.

Ultralow is faint, incomplete membrane staining in 10 percent or fewer of tumour cells, a sub-band of the ASCO/CAP 0 score. DESTINY-Breast06 enrolled HER2-low and ultralow HR-positive metastatic breast cancer after endocrine therapy and showed a progression-free survival benefit over chemotherapy; the US label was amended in January 2025 and the FDA companion diagnostic list carries the PATHWAY 4B5 antibody with the detail 'HER2 ultralow expression (IHC 0 with membrane staining)'. Reproducibility between pathologists at this end of the scale is low, which is why re-review of 0 slides is often requested.

Part ofHER2· ERBB2Other readoutsHER2 HER2 IHC 0 HER2 IHC 1+HER2 IHC 2+HER2 IHC 3+HER2 ISH amplified HER2-low 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

If your hormone-receptor-positive breast cancer was scored HER2 0, ask the pathologist whether any membrane staining was seen. If so it is ultralow, and trastuzumab deruxtecan is on label after hormone therapy stops working; if there was none, it is not.

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

IHC 0 with faint, incomplete membrane staining in 10 percent or fewer of tumour cells; distinguished from IHC 0 with no staining.

“HER2 ultralow expression (IHC 0 with membrane staining)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
IHC 0 with membrane staining, HR-positive, after endocrine therapy	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.