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Objectives  The molecular subtype plays an important role in breast cancer, which is the main reference to guide treatment and is closely related to prognosis. The objective of this study was to explore the potential of the non-contrast-enhanced chest CT-based radiomics to predict breast cancer molecular subtypes non-invasively.    Methods  A total of 300 breast cancer patients (153 luminal types and 147 non-luminal types) who underwent routine chest CT examination were included in the study, of which 220 cases belonged to the training set and 80 cases to the time-independent test set. Identification of the molecular subtypes is based on immunohistochemical staining of postoperative tissue samples. The region of interest (ROI) of breast masses was delineated on the continuous slices of CT images. Forty-two models to predict the luminal type of breast cancer were established by the combination of six feature screening methods and seven machine learning classifiers; 5-fold cross-validation (cv) was used for internal validation. Finally, the optimal model was selected for external validation on the independent test set. In addition, we also took advantage of SHapley Additive exPlanations (SHAP) values to make explanations of the machine learning model.    Results  During internal validation, the area under the curve (AUC) values for different models ranged from 0.599 to 0.842, and the accuracy ranged from 0.540 to 0.775. Eventually, the LASSO_SVM combination was selected as the final model, which included 9 radiomics features. The AUC, accuracy, sensitivity, and specificity of the model to distinguish luminal from the non-luminal type were 0.842 [95% CI: 0.728−0.957], 0.773, 0.818, and 0.773 in the training set and 0.757 [95% CI: 0.640–0.866], 0.713, 0.767, and 0.676 in the test set.    Conclusion  The radiomics based on chest CT may provide a new idea for the identification of breast cancer molecular subtypes.

Potential of the Non-Contrast-Enhanced Chest CT Radiomics to Distinguish Molecular Subtypes of Breast Cancer: A Retrospective Study