Understanding the molecular subtypes of breast cancer is crucial for advancing targeted therapies and precision medicine. For the BRCA molecular subtype prediction problem, this study employs miRGediNET, a machine-learning approach that integrates data from miRTarBase, DisGeNET, and HMDD databases to investigate shared gene associations between microRNA (miRNA) activity and disease mechanisms. Using the BRCA LumAB_Her2Basal dataset, we evaluate miRGediNET’s performance against traditional feature selection methods, including CMIM, mRmR, Information Gain (IG), SelectKBest (SKB), Fast Correlation-Based Filter (FCBF), and XGBoost (XGB). These feature selection techniques were assessed using various classification algorithms including Random Forest (RF), Support Vector Machine (SVM), LogitBoost, Decision Tree, and AdaBoost, all executed with default parameters. The feature selection methods were tested using Monte Carlo Cross-Validation, where performance metrics obtained for each iteration were averaged to ensure robustness. Our findings reveal that miRGediNET outperforms traditional methods in accuracy and Area Under the Curve (AUC), emphasizing its superior capability to identify key genes that bridge miRNA interactions and breast cancer mechanisms. Notably, both miRGediNET and Information Gain (IG) feature selection consistently identified ESR1, a critical biomarker frequently reported in recent research associated with breast cancer prognosis and resistance to endocrine therapies. This integrative approach provides deeper biological insights into miRNA-disease interactions, paving the way for enhanced patient stratification, biomarker discovery, and personalized medicine strategies. The miRGediNET tool, developed on the KNIME platform, offers a practical resource for further exploration in the field of bioinformatics and oncology.