Abstract
BACKGROUND: Optimizing patient selection for neoadjuvant chemotherapy in patients with breast cancer remains an unmet clinical need. Quantitative features from medical imaging were reported to be predictive of treatment responses. However, the biologic meaning of these latent features is poorly understood, preventing the clinical use of such noninvasive imaging markers. The study aimed to develop a deep learning signature (DLS) from pretreatment magnetic resonance imaging (MRI) for predicting responses to neoadjuvant chemotherapy in patients with breast cancer and to further investigate the biologic meaning of the DLS by identifying its underlying pathways using paired MRI and proteomic sequencing data. METHODS: MRI-based DLS was constructed (radiogenomic training dataset, n = 105) and validated (radiogenomic validation dataset, n = 26) for the prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy. Proteomic sequencing revealed biological functions facilitating pCR (n = 139). Their associations with DLS were uncovered by radiogenomic analysis. RESULTS: The DLS achieved a prediction accuracy of 0.923 with an AUC of 0.958, higher than the performance of the model trained by transfer learning. Cellular membrane formation, endocytosis, insulin-like growth factor binding, protein localization to membranes, and cytoskeleton-dependent trafficking were differentially regulated in patients showing pCR. Oncogenic signaling pathways, features correlated with human phenotypes, and features correlated with general biological processes were significantly correlated with DLS in both training and validation dataset (p.adj < 0.05). CONCLUSIONS: Our study offers a biologically interpretable DLS for the prediction of pCR to neoadjuvant chemotherapy in patients with breast cancer, which may guide personalized medication.