Targeted Therapies for Each Subtype of Breast Cancer

Breast cancer (BC) is a clinically heterogeneous malignancy and a leading cause of cancer-related mortality in women worldwide. It is classified into hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative (TNBC) subtypes based on molecular biomarkers. This heterogeneity drives distinct disease progression and treatment responses, making subtype-specific precision therapy indispensable for improving patient outcomes. While estrogen receptor (ER)-targeting agents and anti-HER2 therapies have achieved notable successes, critical challenges remain, including drug resistance, inadequate biomarkers, and limited therapeutic targets for TNBC. This review comprehensively summarizes recent advances in targeted therapies for major BC subtypes: endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for HR-positive BC; novel antibody‒drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and tyrosine kinase inhibitors (TKIs) for HER2-positive BC; and trophoblast cell-surface antigen 2 (Trop-2) ADCs, immunotherapies, and poly-ADP-ribose polymerase (PARP) inhibitors for TNBC. It also discusses cross-subtype therapeutic platforms (ADCs, PI3K/AKT/mTOR pathway) and emerging modalities (chimeric antigen receptor [CAR] T-cell therapy, proteolysis-targeting chimeras [PROTACs]). By analyzing successes, challenges, and translational potential, this review provides a clear framework for clinicians and researchers, advancing personalized treatment optimization and addressing unmet clinical needs in BC precision oncology.