Vision Transformers for Breast Cancer Human Epidermal Growth Factor Receptor 2 Expression Staging without Immunohistochemical Staining

Abstract

Accurate staging of human epidermal growth factor receptor 2 (HER2) expression is vital for evaluating breast cancer treatment efficacy. However, it typically involves costly and complex immunohistochemical staining, along with hematoxylin and eosin staining. This work presents customized vision transformers for staging HER2 expression in breast cancer using only hematoxylin and eosin-stained images. The proposed algorithm comprised three modules: a localization module for weakly localizing critical image features using spatial transformers, an attention module for global learning via vision transformers, and a loss module to determine proximity to a HER2 expression level based on input images by calculating ordinal loss. Results, reported with 95% CIs, reveal the proposed approach's success in HER2 expression staging: area under the receiver operating characteristic curve, 0.9202 ± 0.01; precision, 0.922 ± 0.01; sensitivity, 0.876 ± 0.01; and specificity, 0.959 ± 0.02 over fivefold cross-validation. Comparatively, this approach significantly outperformed conventional vision transformer models and state-of-the-art convolutional neural network models (P < 0.001). Furthermore, it surpassed existing methods when evaluated on an independent test data set. This work holds great importance, aiding HER2 expression staging in breast cancer treatment while circumventing the costly and time-consuming immunohistochemical staining procedure, thereby addressing diagnostic disparities in low-resource settings and low-income countries.