Leveraging Transfer Learning and Multiple Instance Learning for HER2 Automatic Scoring of H\&E Whole Slide Images

Expression of human epidermal growth factor receptor 2 (HER2) is an important biomarker in breast cancer patients who can benefit from cost-effective automatic Hematoxylin and Eosin (H\&E) HER2 scoring. However, developing such scoring models requires large pixel-level annotated datasets. Transfer learning allows prior knowledge from different datasets to be reused while multiple-instance learning (MIL) allows the lack of detailed annotations to be mitigated. The aim of this work is to examine the potential of transfer learning on the performance of deep learning models pre-trained on (i) Immunohistochemistry (IHC) images, (ii) H\&E images and (iii) non-medical images. A MIL framework with an attention mechanism is developed using pre-trained models as patch-embedding models. It was found that embedding models pre-trained on H\&E images consistently outperformed the others, resulting in an average AUC-ROC value of $0.622$ across the 4 HER2 scores ($0.59-0.80$ per HER2 score). Furthermore, it was found that using multiple-instance learning with an attention layer not only allows for good classification results to be achieved, but it can also help with producing visual indication of HER2-positive areas in the H\&E slide image by utilising the patch-wise attention weights.