Abstract
Background: Breast cancer is one of the leading causes of death in female cancer patients. The disease can be detected early using Mammography, an effective X-ray imaging technology. The most important step in mammography is the classification of mammogram patches as benign or malignant. Classically, benign or malignant breast tumors are diagnosed by radiologists' interpretation of mammograms based on clinical parameters. However, because masses are heterogeneous, clinical parameters supply limited information on mammography mass. Therefore, this study aimed to predict benign or malignant breast masses using a combination of image biomarkers and clinical parameters. Methods: We trained a deep learning (DL) fusion network of VGG16 and Inception-V3 network in 5,996 mammography images from the training cohort; DL features were extracted from the second fully connected layer of the DL fusion network. We then developed a combined model incorporating DL features, hand-crafted features, and clinical parameters to predict benign or malignant breast masses. The prediction performance was compared between clinical parameters and the combination of the above features. The strengths of the clinical model and the combined model were subsequently validated in a test cohort (n = 244) and an external validation cohort (n = 100), respectively. Results: Extracted features comprised 30 hand-crafted features, 27 DL features, and 5 clinical features (shape, margin type, breast composition, age, mass size). The model combining the three feature types yielded the best performance in predicting benign or malignant masses (AUC = 0.961) in the test cohort. A significant difference in the predictive performance between the combined model and the clinical model was observed in an independent external validation cohort (AUC: 0.973 vs. 0.911, p = 0.019). Conclusion: The prediction of benign or malignant breast masses improves when image biomarkers and clinical parameters are combined; the combined model was more robust than clinical parameters alone.