Omission of Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: Expanding Evidence in Clinically Node-Negative and Neoadjuvant Therapy Responders

Abstract

Management of the axilla in early-stage breast cancer has progressively evolved toward less invasive approaches, as advances in tumor biology, imaging, and local and systemic therapies have improved outcomes while highlighting the morbidity associated with axillary surgery. Sentinel lymph node biopsy, once considered essential for staging, is increasingly being questioned in select patients with clinically node-negative disease. This review summarizes current evidence evaluating omission of sentinel lymph node biopsy in early-stage breast cancer, including its impact on oncologic outcomes, quality of life, and implementation in clinical practice. Multiple retrospective studies and randomized controlled trials have demonstrated that omission of axillary surgery does not compromise survival outcomes in carefully selected patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. These findings informed the 2016 Choosing Wisely^® recommendation by the Society of Surgical Oncology to avoid routine sentinel lymph node biopsy in women over 70 years of age with clinically node-negative disease. While implementation of this guideline was slower than expected, subsequent studies have explored whether sentinel lymph node biopsy can be safely omitted in a broader group of women with early-stage, HR-positive/HER2-negative invasive breast cancers, who are clinically node-negative on physical exam and preoperative axillary ultrasound. This led to the development of several prospective trials, including SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound), INSEMA (Intergroup Sentinel Mamma), NAUTILUS (No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy), BOOG 2013-08 (Dutch Breast Cancer Research Group 2013-08), OMSLNB (Omission of Sentinel Lymph Node Biopsy), VENUS, and SOAPET (Sentinel node biopsy vs. observation after axillary PET). While many of these trials remain ongoing, results of the SOUND and INSEMA trials demonstrate no difference in survival outcomes following omission of sentinel lymph node biopsy in postmenopausal women with low grade, HR-positive/HER2-negative tumors less than 2 cm in size, and these findings are increasingly being incorporated into clinical practice. Advancements in neoadjuvant therapies have resulted in increasing rates of pathologic complete response in the breast in clinically node-negative women with HER2-positive and triple-negative breast cancers, raising the possibility that sentinel lymph node biopsy may be safely omitted in this population as well. This is being investigated in the EUBREAST-01 (European Breast Cancer Research Association of Surgical Trialists), ASICS (Avoiding Sentinel lymph node biopsy In select Clinical node negative breast cancer patients after neoadjuvant Systemic therapy), ASLAN (Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy), and Neo-NAUTILUS trials. While these trials are ongoing, the results are promising to change the scope of current clinical practice and reduce the morbidity associated with axillary surgery in appropriately selected patients with breast cancer.