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A HER2 mutation is a change in the gene's kinase domain, most often an exon 20 insertion, found in about 2 to 3 percent of lung adenocarcinomas. It is a different thing from HER2 amplification or overexpression, and it selects trastuzumab deruxtecan and, since 2025, zongertinib in lung cancer.
Activating ERBB2 mutations cluster in the tyrosine kinase domain (exons 18 to 21), the commonest being the exon 20 insertion A775_G776insYVMA; they are detected by sequencing of tumour tissue or plasma. Trastuzumab deruxtecan's label covers unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations in tumour or plasma specimens after prior systemic therapy (DESTINY-Lung02). Zongertinib (Hernexeos), approved in 2025, is labelled for non-squamous NSCLC with HER2 (ERBB2) tyrosine kinase domain activating mutations detected by an FDA-authorised test, testing plasma first and tissue if plasma is negative. The FDA list carries the Oncomine Dx Target Test and Guardant360 CDx for both drugs.
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.
A HER2 mutation in lung cancer is found by a gene sequencing test, not by the HER2 stain used in breast cancer. If your report shows one, zongertinib is an on-label first treatment and trastuzumab deruxtecan is on label after prior treatment. If only a blood test was done and it was negative, the label asks for the tumour tissue to be tested too.
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.
Presence of an activating ERBB2 mutation (single nucleotide variants in exons 18 to 21 of the tyrosine kinase domain or exon 20 insertions) by sequencing of tumour tissue or plasma; a negative plasma result should be followed by tissue testing.
“ERBB2/HER2 activating mutations (SNVs in exons 18-21 within the tyrosine kinase domain and exon 20 insertions)”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| Activating HER2 (ERBB2) mutation, tumour or plasma | Trastuzumab deruxtecan | Non-small-cell lung cancer | FDA | label |
| HER2 (ERBB2) tyrosine kinase domain activating mutation | Zongertinib | Non-small-cell lung cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| Oncomine Dx Target Test | Life Technologies (Thermo Fisher Scientific) | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Trastuzumab deruxtecan | P160045/S035 (08/11/2022) |
| Guardant360 CDx | Guardant Health | Non-Small Cell Lung Cancer (NSCLC) - Plasma | Trastuzumab deruxtecan | P200010/S008 (08/11/2022) |
| Oncomine Dx Target Test | Life Technologies (Thermo Fisher Scientific) | Non-Small Cell Lung cancer (NSCLC) - Tissue | Zongertinib | P160045/S049 (08/08/2025) |
| Guardant360 CDx | Guardant Health | Non-small cell lung cancer (NSCLC) - Plasma | Zongertinib | P200010/S027 (06/10/2026) |
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.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.
Shares HER2 ISH amplified (ERBB2 gene amplification), HER2 testing in biliary tract cancer (IHC, ISH and NGS), HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan and the tags biomarker, her2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares EGFR exon 20 insertion, Oncomine Dx Target Test, Genomic and evolutionary classification of lung cancer in never smokers, Guardant360 CDx and the tag biomarker.
Shares Oncomine Dx Target Test, NRG1 gene fusion, Non-small-cell lung cancer and the tag biomarker.
Shares Oncomine Dx Target Test, NRG1 gene fusion, Non-small-cell lung cancer and the tag biomarker.