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

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: HER2-low breast cancer; HER2-low readout; IHC 1+ or 2+/ISH-; HER2 low expression; HER2-low (IHC 1+ or IHC 2+/ISH-)
- Tags: biomarker; her2

## Notes

- Triple-negative breast cancer: DESTINY-Breast04 defined HER2-low as IHC 1+ or IHC 2+ with negative in situ hybridisation and enrolled 63 hormone receptor-negative patients among 557 (Modi 2022); the label covers them after one line of chemotherapy for metastatic disease. HER2-low is 36.6% of TNBC (Schettini 2021), 34.0% of hormone receptor-negative trial patients (Denkert 2021) and 24.0% of untreated TNBCs (Boissiere-Michot 2026). Reproducibility at the 0 versus 1+ boundary is poor, so a second read of a HER2 0 slide is worthwhile before ruling trastuzumab deruxtecan out.

## 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 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 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/), [HER2-ultralow (IHC 0 with membrane staining)](https://onco.cc/biomarkers/her2-ultralow/)
- 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/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [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: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- 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/), [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/)

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