NACNet: A histology context-aware transformer graph convolution network for predicting treatment response to neoadjuvant chemotherapy in Triple Negative Breast Cancer

Neoadjuvant chemotherapy (NAC) response prediction for triple negative breast cancer (TNBC) patients is a challenging task clinically as it requires understanding complex histology interactions within the tumor microenvironment (TME). Digital whole slide images (WSIs) capture detailed tissue information, but their giga-pixel size necessitates computational methods based on multiple instance learning, which typically analyze small, isolated image tiles without the spatial context of the TME. To address this limitation and incorporate TME spatial histology interactions in predicting NAC response for TNBC patients, we developed a histology context-aware transformer graph convolution network (NACNet). Our deep learning method identifies the histopathological labels on individual image tiles from WSIs, constructs a spatial TME graph, and represents each node with features derived from tissue texture and social network analysis. It predicts NAC response using a transformer graph convolution network model enhanced with graph isomorphism network layers. We evaluate our method with WSIs of a cohort of TNBC patient (N=105) and compared its performance with multiple state-of-the-art machine learning and deep learning models, including both graph and non-graph approaches. Our NACNet achieves 90.0% accuracy, 96.0% sensitivity, 88.0% specificity, and an AUC of 0.82, through eight-fold cross-validation, outperforming baseline models. These comprehensive experimental results suggest that NACNet holds strong potential for stratifying TNBC patients by NAC response, thereby helping to prevent overtreatment, improve patient quality of life, reduce treatment cost, and enhance clinical outcomes, marking an important advancement toward personalized breast cancer treatment.