HER2-low (IHC 1+ or IHC 2+/ISH-negative)

aka HER2-low breast cancer, HER2-low readout, IHC 1+ or 2+/ISH-, HER2 low expression, HER2-low (IHC 1+ or IHC 2+/ISH-)

HER2-low is not a new stain but a new reading of the old one: 1+ or 2+ without gene amplification. It covers about half of breast cancers and makes them eligible for trastuzumab deruxtecan.

HER2-low is defined in the trastuzumab deruxtecan label as IHC 1+ or IHC 2+ with a negative in situ hybridisation result, determined by an FDA-authorised test. DESTINY-Breast04 (2022) established the category in metastatic breast cancer after one or two lines of chemotherapy, and DESTINY-Breast06 (2025) extended it, with HER2-ultralow, to HR-positive disease after endocrine therapy. The FDA companion diagnostic list carries the PATHWAY 4B5 antibody with the detail 'HER2-low expression (IHC 1+ or IHC 2+/ISH non-amplified)'. Outside breast cancer HER2-low is a trial category, not a label one.

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

If your breast cancer report says 1+, or 2+ with a negative ISH, it is HER2-low. That does not change first treatment, but once the cancer has spread and chemotherapy (or, for hormone-receptor-positive cancers, hormone therapy) has stopped working, trastuzumab deruxtecan is an on-label option. A report written before 2022 may only say 'HER2-negative'; the underlying score can be looked up.

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 1+, or IHC 2+ with a non-amplified in situ hybridisation result, by an FDA-authorised HER2 assay.

“HER2-low expression (IHC 1+ or IHC 2+/ISH non-amplified)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
IHC 1+ or IHC 2+/ISH-	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/S047 (09/30/2022)
VENTANA HER2 Dual ISH DNA Probe Cocktail	Ventana Medical Systems (Roche)	Breast Cancer - Tissue	Trastuzumab deruxtecan	P190031/S015 (05/15/2026)

Tests that measure it

HercepTest PATHWAY anti-HER2/neu (4B5)HER2 IQFISH pharmDx and INFORM HER2 Dual ISH

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.