Advances in Systemic Treatment of Breast Cancer.

Systemic therapy for breast cancer has evolved rapidly since 2020, driven by the expansion of targeted therapies, antibody-drug conjugates, and immunotherapy across biologic subtypes. The integration of tumor molecular profiling and germline testing has enabled increasingly personalized, biomarker-guided treatment strategies. In hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, cyclin-dependent kinase 4 and 6 inhibitors remain foundational, whereas phosphatidylinositol 3-kinase pathway inhibitors, oral selective estrogen-receptor degraders, and antibody-drug conjugates have transformed disease management after endocrine resistance. In HER2-positive disease, antibody-drug conjugates - particularly trastuzumab deruxtecan - have improved outcomes and are being used in earlier lines of therapy, a development that is reshaping treatment paradigms. In triple-negative breast cancer, immune checkpoint inhibitors have improved outcomes in both metastatic and early-stage disease. Across subtypes, advances in curative therapy increasingly emphasize risk-adapted escalation and de-escalation of treatment. Ongoing challenges include improving treatment sequencing, identifying predictive biomarkers, integrating emerging tools such as analysis of circulating tumor DNA, and ensuring equitable access to high-cost therapies.