# HER2-low scoring → T-DXd

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

## TL;DR

Reading the faint end of the HER2 stain decides who gets Enhertu.

## Summary

This diagnostic-therapeutic pairing links Histopathology & immunohistochemistry scoring of HER2 to treatment with Trastuzumab deruxtecan (T-DXd): reading the faint end of the HER2 stain decides who gets Enhertu. The rationale is that the bystander payload needs only minimal antigen for uptake, so the immunohistochemistry cut-off is a delivery threshold rather than a driver threshold. In the phase 3 DESTINY-Breast04 and DESTINY-Breast06 trials, HER2-low (IHC 1+ or 2+) and HER2-ultralow (IHC 0 with faint staining) tumours predicted T-DXd benefit in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). Reproducibility at the low end is poor, so AI-assisted HER2 scoring is being validated, as pursued in the idea AI quantification of HER2-low and HER2-ultralow.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Histopathology & immunohistochemistry + Trastuzumab deruxtecan
- Type: diagnostic-therapeutic
- Rationale: Bystander payload needs only minimal antigen for uptake; IHC cut-off is a delivery threshold not a driver threshold.
- Evidence: Phase 3 (DESTINY-Breast04/06).

## Sources

- ClinicalTrials.gov NCT03734029: DESTINY-Breast04: https://clinicaltrials.gov/study/NCT03734029
- ClinicalTrials.gov NCT04494425: DESTINY-Breast06: https://clinicaltrials.gov/study/NCT04494425

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/)
- trials: [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/), [DESTINY-Breast06](https://onco.cc/trials/destiny-breast06/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- drugs: [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- ideas: [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/)

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