# Calibrated reference slides so every lab scores HER2-low the same way

Source: https://onco.cc/ideas/idea-tr2-her2-low-reference-materials/  
OnCo record `idea-tr2-her2-low-reference-materials` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Whether a breast cancer counts as HER2-low, and so qualifies for trastuzumab deruxtecan, turns on the least reproducible step of the HER2 stain, score 1+ versus 0. Cell-line microarrays with a known quantity of HER2 protein per cell, run alongside clinical slides, would anchor every laboratory to a physical standard.

## Summary

T-DXd approval for HER2-low created a treatment decision at IHC 1+ versus 0, the least reproducible part of the HER2 scale, with inter-pathologist agreement reported as poor. Cell-line microarrays with quantified HER2 protein per cell, distributed as reference materials and run alongside clinical slides (as NordiQC and CAP do for proficiency testing), would anchor staining intensity and scoring to a physical standard, complemented by digital image analysis calibrated to the same materials.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Laboratories using calibrated reference materials will show inter-laboratory agreement on HER2 0 versus 1+ above 85%, compared with the 60 to 70% reported in current concordance studies.
- Rationale: Reference materials transformed reproducibility in clinical chemistry. Pathology has proficiency schemes but few quantitative anchors for low-level protein expression.
- Proposed test: Distribute reference arrays to 50 laboratories with a blinded set of clinical cases; measure agreement with and without reference calibration.
- Maturity: early-clinical
- Actor: regulator

## Sources

- NordiQC: https://www.nordiqc.org/

## Connected records

- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- ideas: [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/), [Publish each laboratory's biomarker proficiency results](https://onco.cc/ideas/idea-tr2-eqa-public-results/)
- technologies: [Digital pathology & AI](https://onco.cc/technologies/digital-pathology-ai/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- drugs: [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- trials: [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/), [DESTINY-Breast06](https://onco.cc/trials/destiny-breast06/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)
- key papers: [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/)

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