Abstract
Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women and the leading cause of cancer-related deaths globally. Molecular subtyping is crucial for prognosis and treatment planning, with immunohistochemistry (IHC) being the most commonly used method. However, IHC has limitations, including observer variability, a lack of standardization, and a lack of reproducibility. Gene expression profiling is considered the ground truth for molecular subtyping; unfortunately, this is expensive and inaccessible to many institutions. This study investigates the potential of an artificial intelligence (AI) model to predict BC molecular subtypes directly from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). Methods: A pretrained deep learning framework based on multiple-instance learning (MIL) was validated on the Stavanger Breast Cancer (SBC) dataset, consisting of 538 BC cases. Three classification tasks were assessed, including two-class [triple negative BC (TNBC) vs. non-TNBC], three-class (luminal vs. HER2-positive vs. TNBC), and four-class (luminal A vs. luminal B vs. HER2-positive vs. TNBC) groups. Performance metrics were used for the evaluation of the AI model. Results: The AI model demonstrated strong performance in distinguishing TNBC from non-TNBC (AUC = 0.823, accuracy = 0.833, F1-score = 0.824). However, performance declined with an increasing number of classes. Conclusions: The study highlights the potential of AI in BC molecular subtyping from H&E WSIs, offering an easily applicable and standardized method to IHC. Future improvements should focus on optimizing multi-class classification and validating AI-based methods against gene expression analyses for enhanced clinical applicability.