Unsupervised Analysis Based on DCE-MRI Radiomics Features Revealed Three Novel Breast Cancer Subtypes with Distinct Clinical Outcomes and Biological Characteristics.

Background: This study aimed to reveal the heterogeneity of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast cancer (BC) and identify its prognosis values and molecular characteristics. Methods: Two radiogenomics cohorts (n = 246) were collected and tumor regions were segmented semi-automatically. A total of 174 radiomics features were extracted, and the imaging subtypes were identified and validated by unsupervised analysis. A gene-profile-based classifier was developed to predict the imaging subtypes. The prognostic differences and the biological and microenvironment characteristics of subtypes were uncovered by bioinformatics analysis. Results: Three imaging subtypes were identified and showed high reproducibility. The subtypes differed remarkably in tumor sizes and enhancement patterns, exhibiting significantly different disease-free survival (DFS) or overall survival (OS) in the discovery cohort (p = 0.024) and prognosis datasets (p ranged from <0.0001 to 0.0071). Large sizes and rapidly enhanced tumors usually had the worst outcomes. Associations were found between imaging subtypes and the established subtypes or clinical stages (p ranged from <0.001 to 0.011). Imaging subtypes were distinct in cell cycle and extracellular matrix (ECM)-receptor interaction pathways (false discovery rate, FDR < 0.25) and different in cellular fractions, such as cancer-associated fibroblasts (p < 0.05). Conclusions: The imaging subtypes had different clinical outcomes and biological characteristics, which may serve as potential biomarkers.