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Modern Management of the Axilla in HER2-Negative Hormone Receptor-Positive Early Breast Cancer Upfront Surgery: Toward De-Escalation and Individualization
by
, , , and
Halima Abahssain
1,2,*
,
David Pasquier
3,4
,
Khaoula Laabid
3,5,
Meryem Barani
1,
Sébastien Borges
1,
Stephen Poitureau
1,
Ghizlane Bettache
1,
Thi-Lan-Anh Nguyen
1,
Mbolam Bytha
1,
Joseph Rodriguez
1,
Antoine Lemaire
6
,
Giuseppe Curigliano
7 and
Amine Souadka
2,8 1
Oncology and Medical Specialties Department, Valenciennes General Hospital, 59300 Valenciennes, France
2
Equipe de Recherche en Oncologie Translationnelle (EROT), Faculty of Medicine and Pharmacy, University Mohammed V in Rabat, Rabat 10100, Morocco
3
Academic Department of Radiation Oncology, Centre Oscar Lambret, 59000 Lille, France
4
CNRS, Centrale Lille, UMR 9189–CRIStAL, University of Lille, 59000 Lille, France
5
Radiation Oncology Department, Mohammed VI University Hospital, Marrakesh 40000, Morocco
6
Supportive Care Department, Valenciennes General Hospital, 59300 Valenciennes, France
7
Department of Oncology and Hemato-Oncology, University of Milan, 20133 Milan, Italy
8
Surgical Oncology Department, National Institute of Oncology, University Mohammed V in Rabat, Rabat 10100, Morocco
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(1), 131; https://doi.org/10.3390/cancers18010131 (registering DOI)
Submission received: 30 November 2025
/
Revised: 25 December 2025
/
Accepted: 26 December 2025
/
Published: 30 December 2025
(This article belongs to the Special Issue De-escalation of Axillary and Breast Cancer Surgery in the Setting of Neo-Adjuvant Chemotherapy)
Simple Summary
Axillary management in HER2-negative, hormone receptor-positive early breast cancer has shifted toward surgical de-escalation, supported by randomized trials demonstrating that completion ALND can be safely omitted in selected patients with limited nodal involvement, particularly when radiotherapy or genomic risk profiling is integrated. Systemic treatment strategies increasingly incorporate nodal burden and biologic profil to guide adjuvant therapy decisions, while predictive tools and high-resolution axillary ultrasound help estimate additional nodal involvement without routine dissection. At the same time, the therapeutic benefit of CDK4/6 and PARP inhibitors must be balanced against substantial risks of severe arm morbidity when ALND is used solely to meet drug-eligibility thresholds. A multidisciplinary, risk-adapted approach that integrates tumor biology, imaging, predictive modeling, minimal residual disease assessment, and patient preferences is now central to delivering individualized care while minimizing morbidity and preserving oncologic safety.
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.
