# HER2-ultralow (IHC 0 with membrane staining)

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: HER2-ultralow; HER2 ultralow; ultralow; IHC 0 with faint staining; IHC >0 <1+
- Tags: biomarker; her2

## Notes

- Triple-negative breast cancer: ultralow (IHC 0 with faint incomplete membrane staining in 10% or fewer cells) was 37.6% of 367 untreated TNBCs, with 38.4% null (Boissiere-Michot 2026). DESTINY-Breast06 enrolled hormone receptor-positive disease only, so the ultralow label does not extend to TNBC; ultralow status carried no prognostic weight in TNBC.

## Sources

- ENHERTU prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6

## Connected records

- biomarkers: [HER2 IHC 0 (HER2-negative, including ultralow)](https://onco.cc/biomarkers/her2-ihc-0/), [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/), [HER2-low (IHC 1+ or IHC 2+/ISH-negative)](https://onco.cc/biomarkers/her2-low-ihc/)
- cancers: [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/), [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: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- key papers: [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/), [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/)
- targets: [HER2](https://onco.cc/targets/her2/)
- 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: [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/)

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