Multiparametric MRI model to predict molecular subtypes of breast cancer using Shapley additive explanations interpretability analysis

The purpose of this study was to assess the predictive performance of multiparametric magnetic resonance imaging (MRI) for molecular subtypes and interpret features using SHapley Additive exPlanations (SHAP) analysis. Patients with breast cancer who underwent pre-treatment MRI (including ultrafast dynamic contrast-enhanced MRI, magnetic resonance spectroscopy, diffusion kurtosis imaging and intravoxel incoherent motion) were recruited between February 2019 and January 2022. Thirteen semantic and thirteen multiparametric features were collected and the key features were selected to develop machine-learning models for predicting molecular subtypes of breast cancers (luminal A, luminal B, triple-negative and HER2-enriched) by using stepwise logistic regression. Semantic model and multiparametric model were built and compared based on five machine-learning classifiers. Model decision-making was interpreted using SHAP analysis. A total of 188 women (mean age, 53 ± 11 [standard deviation] years; age range: 25–75 years) were enrolled and further divided into training cohort (131 women) and validation cohort (57 women). XGBoost demonstrated good predictive performance among five machine-learning classifiers. Within the validation cohort, the areas under the receiver operating characteristic curves (AUCs) for the semantic models ranged from 0.693 (95% confidence interval [CI]: 0.478–0.839) for HER2-enriched subtype to 0.764 (95% CI: 0.681–0.908) for luminal A subtype, inferior to multiparametric models that yielded AUCs ranging from 0.771 (95% CI: 0.630–0.888) for HER2-enriched subtype to 0.857 (95% CI: 0.717–0.957) for triple-negative subtype. The AUCs between the semantic and the multiparametric models did not show significant differences (P range: 0.217–0.640). SHAP analysis revealed that lower iAUC, higher kurtosis, lower D*, and lower kurtosis were distinctive features for luminal A, luminal B, triple-negative breast cancer, and HER2-enriched subtypes, respectively. Multiparametric MRI is superior to semantic models to effectively predict the molecular subtypes of breast cancer.