OnCo
ideasIdea

AI quantification of HER2-low and HER2-ultralow

Pathologists disagree about faint HER2 staining, yet that decision unlocks Enhertu. Let a validated algorithm do the counting.

Concordance for HER2 0 vs 1+ is poor (~25-50% agreement in some studies). AI-assisted scoring improves reproducibility and can quantify membrane staining continuously rather than in bins.

Confidence
50%75%likelyOnCo editors (initial estimate), 2026-09-07 · Reproducibility gains are near-certain; predictive superiority is the question.
Hypothesis
A continuous AI-derived HER2 membrane score predicts T-DXd benefit better than pathologist-assigned IHC categories, and reclassifies a meaningful fraction of IHC 0 tumours as eligible.
Rationale
T-DXd benefit depends on a delivery threshold, which is continuous; discretised human scoring loses information.
What would test it
Run a retrospective analysis of DESTINY-Breast04/06 slides with an AI scorer, then prospective companion-diagnostic validation.
Maturity
early clinical

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