A small HER2 reader for routine H&E slides: real-world deployment

Abstract

HER2 status decides who receives HER2-targeted therapy. Pathologists score HER2 protein by immunohistochemistry (IHC); equivocal IHC 2+ tumours, their hardest calls, wait for in situ hybridisation (ISH). We built a HER2 reader for routine H&E slides, owned end to end, as a baseline for pathologists. A 22M-parameter ViT-S/16 tile encoder was trained on public TCGA slides by self-supervision, distillation from H-optimus-0 and two rounds of JEPA refinement; five cross-validated attention-based slide classifiers average their probabilities; and an operating point is fixed on training data. Compared under one paired ten-seed protocol, readers on our encoder rank first of 7 on external validation from TCGA-BRCA to Yale-HER2 (AUC 0.812), level with readers on encoders 4 and 50 times larger. We also rebuilt PathBench's encoder benchmark on public cohorts; our replica reproduces its published order of reference encoders, and under it our encoder ranks first of 7 on TCGA-BRCA (0.689) and sits level with H-optimus-0 and Phikon on Yale-HER2 (0.897). On three external hospitals our deployed reader reaches AUC 0.82 on Yale-HER2 (about 0.81 with training slides balanced for tissue size), 0.75 on HEROHE and 0.63 on BCNB biopsies, and among HEROHE's 85 IHC 2+ cases it ranks ISH-amplified above non-amplified tumours at 0.76, best among our TCGA-trained readers. Per-laboratory score normalisation and a laboratory's own slides improve it further on a new site. Without a GPU our reader needs 5-6 s per slide. It serves as a research-use pre-read in a pathology platform, where it proposes a probability and a call beside IHC and helps prioritise ISH for equivocal cases. Weights, per-slide predictions and the data behind every figure are public at https://huggingface.co/cloudkites/her2-reader.