Advances in Molecular Subtype-Based Precision Therapy and Strategies to Overcome Resistance in Breast Cancer

Abstract

Breast cancer is a leading cause of cancer -related morbidity and mortality, characterized by significant biological and molecular heterogeneity. Molecular subtypes —including luminal A, luminal B, HER2 - enriched, and triple -negative—inform prognosis and guide prec ision therapies. Despite advances with endocrine agents, HER2-targeted therapies, PARP inhibitors, and immune checkpoint inhibitors, therapeutic resistance remains a major challenge, driven by intratumoral heterogeneity, cancer stem cell plasticity, and tumor microenvironmental factors. Genomic profiling, liquid biopsies, combination and adaptive strategies, and next-generation antibody-drug conjugates are emerging to overcome resistance and optimize outcomes. Additionally, novel immunotherapies and artific ial intelligence (AI) –assisted decision -making support individualized treatment selection. This review summarizes recent advances, from molecular characterization to precision-guided interventions and strategies to counteract resistance, and emphasizes the integration of biological insights into personalized breast cancer management.