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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.
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.
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.
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| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| IHC 1+ or IHC 2+/ISH- | Trastuzumab deruxtecan | HER2-low and HER2-ultralow metastatic breast cancer | FDA | label |
| 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) |
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.
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
The trial-grade HER2-low share for TNBC is about a third, and the survival difference hints that HER2-zero triple-negative disease is the more aggressive group.
HER2-low is a drug eligibility label, not a biological subtype, in triple-negative disease; because a third of patients qualify for trastuzumab deruxtecan on a score pathologists disagree about, re-scoring and digital assistance for HER2 0 versus 1+ is a practical gap.
Shares HER2 IHC 2+ (equivocal, reflex to ISH), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry), FISH / ISH (in situ hybridisation) and the tags biomarker, her2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares HER2-ultralow (IHC 0 with membrane staining), Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, HER2-low and HER2-ultralow metastatic breast cancer.
Shares HER2-low and HER2-ultralow, Immunohistochemistry (IHC), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Immunohistochemistry (IHC) and the tag biomarker.
Shares Immunohistochemistry (IHC), Breast cancer (all types), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Immunohistochemistry (IHC), Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.