PhiHER2: phenotype-informed weakly supervised model for HER2 status prediction from pathological images

Abstract

Motivation Human epidermal growth factor receptor 2 (HER2) status identification enables physicians to assess the prognosis risk and determine the treatment schedule for patients. In clinical practice, pathological slides serve as the gold standard, offering morphological information on cellular structure and tumoral regions. Computational analysis of pathological images has the potential to discover morphological patterns associated with HER2 molecular targets and achieve precise status prediction. However, pathological images are typically equipped with high-resolution attributes, and HER2 expression in breast cancer (BC) images often manifests the intratumoral heterogeneity. Results We present a phenotype-informed weakly supervised multiple instance learning architecture (PhiHER2) for the prediction of the HER2 status from pathological images of BC. Specifically, a hierarchical prototype clustering module is designed to identify representative phenotypes across whole slide images. These phenotype embeddings are then integrated into a cross-attention module, enhancing feature interaction and aggregation on instances. This yields a phenotype-based feature space that leverages the intratumoral morphological heterogeneity for HER2 status prediction. Extensive results demonstrate that PhiHER2 captures a better WSI-level representation by the typical phenotype guidance and significantly outperforms existing methods on real-world datasets. Additionally, interpretability analyses of both phenotypes and WSIs provide explicit insights into the heterogeneity of morphological patterns associated with molecular HER2 status. Availability and implementation Our model is available at https://github.com/lyotvincent/PhiHER2

Application of AI in detection of breast cancer with laboratory results monitoring

“…AI has shown promising potential in the detection of human epidermal growth factor receptor 2 (HER2), a protein overexpressed in some breast cancers. By utilizing machine learning algorithms, AI technologies can analyze histopathological images and genetic data to assist in the identification and characterization of HER2positive tumors through the analysis of immunohistochemical (IHC) staining patterns in tissue samples [44].…”