Modern Management of the Axilla in HER2-Negative Hormone Receptor-Positive Early Breast Cancer Upfront Surgery: Toward De-Escalation and Individualization

Abstract

Axillary management in early-stage, HER2-negative, hormone receptor-positive breast cancer has undergone major changes in recent years. While axillary lymph node dissection (ALND) was once considered essential for staging and regional control, increasing evidence supports the safety of surgical de-escalation in selected patients. At the same time, systemic therapies such as CDK4/6 and PARP inhibitors rely on nodal burden to define eligibility, raising new challenges in balancing oncologic benefit with treatment-related morbidity. This narrative review summarizes current strategies in axillary management for patients undergoing upfront surgery for HR-positive, HER2-negative early breast cancer. It explores the role of sentinel lymph node biopsy (SLNB), the indications for ALND, the integration of adjuvant systemic therapy, and the emerging role of radiotherapy and predictive tools in guiding individualized treatment decisions. Key randomized trials including Z0011, AMAROS, SENOMAC, SOUND, and INSEMA have demonstrated that omission of ALND is safe in patients with limited nodal involvement, especially when combined with whole-breast or regional nodal radiotherapy. However, trials such as MonarchE and OlympiA have introduced systemic therapies whose indications are closely tied to nodal status, prompting reconsideration of the extent of axillary staging. Advances in imaging and risk stratification tools offer new avenues for safely limiting surgical intervention while preserving access to systemic options. In conclusion, modern axillary management in HR-positive, HER2-negative breast cancer involves navigating the intersection between de-escalated surgery and risk-adapted systemic therapy. Future strategies should prioritize individualized care, incorporating tumor biology, imaging findings, and patient preferences, with multidisciplinary collaboration playing a central role in optimizing outcomes.