Abstract:Our objective is to show the feasibility of using simulated mammograms to detect mammographically-occult (MO) cancer in women with dense breasts and a normal screening mammogram who could be triaged for additional screening with magnetic resonance imaging (MRI) or ultrasound. We developed a Conditional Generative Adversarial Network (CGAN) to simulate a mammogram with normal appearance using the opposite mammogram as the condition. We used a Convolutional Neural Network (CNN) trained on Radon Cumulative Distribution Transform (RCDT) processed mammograms to detect MO cancer. For training CGAN, we used screening mammograms of 1366 women. For MO cancer detection, we used screening mammograms of 333 women (97 MO cancer) with dense breasts. We simulated the right mammogram for normal controls and the cancer side for MO cancer cases. We created two RCDT images, one from a real mammogram pair and another from a real-simulated mammogram pair. We finetuned a VGG16 on resulting RCDT images to classify the women with MO cancer. We compared the classification performance of the CNN trained on fused RCDT images, CNN_{Fused} to that of trained only on real RCDT images, CNN_{Real}, and to that of trained only on simulated RCDT images, CNN_{Simulated}. The test AUC for CNN_{Fused} was 0.77 with a 95% confidence interval (95CI) of [0.71, 0.83], which was statistically better (p-value < 0.02) than the CNN_{Real} AUC of 0.70 with a 95CI of [0.64, 0.77] and CNN_{Simulated} AUC of 0.68 with a 95CI of [0.62, 0.75]. It showed that CGAN simulated mammograms can help MO cancer detection.