# HER2-low and HER2-ultralow

Source: https://onco.cc/terms/her2-low/  
OnCo record `her2-low` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack.

## Summary

HER2-low describes tumours with a little HER2, scored IHC 1+ or 2+ without gene amplification, and HER2-ultralow describes a trace, scored IHC 0 with faint membrane staining in a small fraction of cells. Older HER2 drugs ignored these tumours, but Trastuzumab deruxtecan can attack them, as DESTINY-Breast04 and DESTINY-Breast06 showed in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). The result redefined what 'HER2-negative' means and put pressure on pathology to score the low end reliably, hence the links to Histopathology & immunohistochemistry, Companion diagnostics, the pairing HER2-low scoring to T-DXd and the idea on AI quantification of HER2-low. It also appears in the bottleneck on biomarker validation and the Giuseppe Curigliano entry.

## Fields

- Kind: Term
- Last checked: 2026-09-04
- Also known as: HER2-low; HER2 low; HER2-ultralow; HER2 ultralow; HER2-ultra-low; HER2 IHC 1+; IHC 1+; IHC 2+ ISH-negative; HER2 IHC 0; HER2-zero; HER2 0; HER2 immunohistochemistry score; HER2-low status

## Notes

- The classification has caught up with the drugs. The sixth edition of the WHO Classification of Tumours of the Breast (April 2026) updates the HER2 reporting categories after DESTINY-Breast04 and DESTINY-Breast06, making the distinction between no membrane staining at all and any membrane staining a reporting requirement rather than a research nicety, because that boundary now decides eligibility for trastuzumab deruxtecan (Quinn 2026).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/HER2
- NCI Dictionary of Cancer Terms: HER2-low breast cancer: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/her2-low-breast-cancer
- Quinn et al., Histopathology 2026;89(2):199 to 218: World Health Organization classification of tumours of the breast, 6th edition 2026: https://doi.org/10.1111/his.70149

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [HER2-low and HER2-ultralow metastatic breast cancer](https://onco.cc/cancers/her2-low-metastatic-breast-cancer/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [Amplification](https://onco.cc/terms/amplification/), [ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)](https://onco.cc/terms/er-pr-negative-threshold/), [HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP](https://onco.cc/terms/her2-testing-uk-breast/), [HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)](https://onco.cc/terms/her2-low-and-trop2-adc-eligibility-tnbc/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [Overexpression](https://onco.cc/terms/overexpression/), [Receptor conversion: when the receptors change between the primary and a recurrence](https://onco.cc/terms/receptor-conversion-breast/), [The WHO classification of breast tumours, and what the 6th edition changed](https://onco.cc/terms/who-breast-classification/)
- trials: [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/), [DESTINY-Breast06](https://onco.cc/trials/destiny-breast06/)
- key papers: [Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials](https://onco.cc/key-papers/paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021/), [Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer](https://onco.cc/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/), [DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group](https://onco.cc/key-papers/paper-destiny-breast04-nejm-2022/), [DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer](https://onco.cc/key-papers/paper-destiny-breast06-nejm-2024/), [Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status](https://onco.cc/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/), [Calibrated reference slides so every lab scores HER2-low the same way](https://onco.cc/ideas/idea-tr2-her2-low-reference-materials/), [Randomised trials to test whether biomarker-negative patients really do not benefit](https://onco.cc/ideas/idea-tr2-biomarker-negative-arms/), [Re-test the metastasis, not the old primary, before every change of treatment](https://onco.cc/ideas/idea-bio1-rebiopsy-before-switch/), [Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan](https://onco.cc/ideas/idea-tnbc-her2-ultralow-testing-uptake/), [Test the drug in biomarker-negative patients too, so the biomarker can be validated](https://onco.cc/ideas/idea-tr2-marker-stratified-default/)
- technologies: [Companion diagnostics](https://onco.cc/technologies/companion-diagnostic/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- pairings: [HER2-low scoring → T-DXd](https://onco.cc/pairings/her2-low-to-tdxd/)
- people: [Giuseppe Curigliano](https://onco.cc/people/giuseppe-curigliano/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Knowledge reaches practice too slowly](https://onco.cc/bottlenecks/b-knowledge-diffusion/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- biomarkers: [HER2 IHC 0 (HER2-negative, including ultralow)](https://onco.cc/biomarkers/her2-ihc-0/), [HER2 IHC 1+](https://onco.cc/biomarkers/her2-ihc-1-plus/), [HER2 IHC 2+ (equivocal, reflex to ISH)](https://onco.cc/biomarkers/her2-ihc-2-plus/), [HER2-low (IHC 1+ or IHC 2+/ISH-negative)](https://onco.cc/biomarkers/her2-low-ihc/), [HER2-ultralow (IHC 0 with membrane staining)](https://onco.cc/biomarkers/her2-ultralow/), [TROP2 expression](https://onco.cc/biomarkers/trop2-expression/)

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JSON: https://onco.cc/api/v1/entities/her2-low.json