ObjectiveTo investigate the value of 18F-FDG PET/CT-based intratumoral and peritumoral radiomics in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.Methods190 patients who met the inclusion and exclusion criteria from 2017 to 2022 were studied. Features were extracted from the PET/CT intratumoral and peritumoral regions, feature selection was performed through the correlation analysis, t-tests, and least absolute shrinkage and selection operator regression (LASSO). Four classifiers, support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), and naive bayes (NB) were used to build the prediction models. The receiver operating characteristic (ROC) curves were plotted to measure the predictive performance of the models. Concurrent stratified analysis was conducted to establish subtype-specific features for each molecular subtype.ResultsCompared to intratumoral features alone, intratumoral + peritumoral features achieved higher AUC values in each classifier. The SVM model constructed with intratumoral + peritumoral features achieved the highest AUC values in both the train and test set (train set: 0.95 and test set: 0.83). Subtype-specific features improve performance in predicting the efficacy of NAC (luminal group: 0.90; HER2 + group: 0.86; triple negative group: 0.92).ConclusionIntratumoral and peritumoral radiomics models based on 18F-FDG PET/CT can reliably forecast the efficacy of NAC, thereby assisting clinical decision-making.