Neoadjuvant systemic therapy and the evolution of axillary management in breast cancer: a mini review and future directions

Neoadjuvant Systemic Therapy (NST) has undergone a remarkable evolution over five decades, evolving from a strategy employed to render inoperable tumors resectable to a therapeutic platform whose post-treatment pathological assessment now serves as a powerful in vivo readout of tumor biology, enabling real-time personalization of both surgical and systemic tumor management. Alongside advances in systemic therapy, our approach to the axilla has been fundamentally transformed. Management of the axilla has evolved from routine axillary lymph node dissection (ALND), regardless of treatment response, to a nuanced, response-adapted surgical approach. This review traces the historical trajectory of NST in breast cancer, with a particular focus on its impact on axillary surgical planning. We examine landmark clinical trials establishing sentinel lymph node biopsy (SLNB) feasibility after NST, the development of targeted axillary dissection (TAD) as a precision staging technique, and the critical role of pathologic complete response (pCR) as both a prognostic endpoint and a surgical decision-making tool. The evidence base for ALND omission across the spectrum of nodal response — from complete sterilization to low-volume residual disease — is examined in depth, alongside the challenges of residual disease management, staging information loss, surgical morbidity, and global disparities in access. Emerging directions including circulating tumor DNA, artificial intelligence-based imaging tools, and novel systemic agents are discussed in the context of an evolving paradigm in which surgical extent is increasingly determined by tumor biology and treatment response rather than anatomical convention.