Redefining the role of anthracyclines in early breast cancer treatment

Anthracyclines have long been a cornerstone of early breast cancer treatment, contributing to significant reductions in recurrence and improvements in survival. Concerns about long-term toxicities, particularly cardiotoxicity and secondary hematologic malignancies, have led to a reevaluation of their role in modern chemotherapy regimens. In this review, we analyze the role of anthracyclines in early-stage breast cancer treatment, focusing on the balance between efficacy and toxicity. The comprehensive patient-level EBCTCG meta-analysis provided robust evidence supporting the superiority of regimens containing anthracyclines and taxanes over taxane-only protocols. Evidence from trials specifically designed to test the non-inferiority of taxane-based regimens compared to anthracycline-containing protocols in HER2-negative breast cancer further supports the benefit of anthracyclines, particularly in hormone receptor-negative patients and those with a high nodal burden. In HER2-positive breast cancer, while the clinical benefit of anthracyclines appears to be more limited, we critically assess the limitations of the existing evidence, noting that most trials were not explicitly designed or powered to evaluate the equivalence of anthracycline-free regimens. We also examine novel targeted therapies, such as HER2-targeted agents and immune checkpoint inhibitors, which have been evaluated in combination with anthracycline-based chemotherapy backbones. Emerging strategies to minimize toxicity, such as predictive biomarkers, molecular profiling for patient selection, and early cardiotoxicity detection methods, are also discussed. We conclude by proposing an individualized, risk-adapted approach to integrating anthracyclines into breast cancer treatment, underscoring the need for careful risk–benefit evaluations, particularly in resource-limited settings, where anthracyclines may still play a pivotal role in achieving optimal outcomes.