Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes
Authors: Gentilini Oreste Davide , Botteri Edoardo , Sangalli Claudia , Galimberti Viviana , Porpiglia Mauro , Agresti Roberto , Luini Alberto , Viale Giuseppe , Cassano Enrico , Peradze Nickolas , Toesca Antonio , Massari Giulia , Sacchini Virgilio , Munzone Elisabetta , Leonardi Maria Cristina , Cattadori Francesca , Di Micco Rosa , Esposito Emanuela , Sgarella Adele , Cattaneo Silvia , Busani Massimo , Dessena Massimo , Bianchi Anna , Cretella Elisabetta , Ripoll Orts Francisco , Mueller Michael , Tinterri Corrado , Chahuan Manzur Badir Jorge , Benedetto Chiara , Veronesi Paolo ,   SOUND Trial Group, Bassi Fabio D. , Borella Fulvio , Caldarella Pietro , Colleoni Marco A. , Corso Giovanni , Dellapasqua Silvia , Ferrari Alberta , Garcia-Etienne Carlos , Gentile Damiano , Germano Alessandro , Grosso Luigi P. , Intra Mattia , Iorfida Monica , Vila Josè , Limite Gennaro , Lissidini Germana , Macellari Giorgio , Magnoni Francesca , Maugeri Ilaria , Mazza Manuelita , Montagna Emilia , Naninato Paola , Nicosia Luca , Orecchia Roberto , Pierini Alberto F. , Rauh Claudia , Rinaldo Massimo , Rotili Anna , Rotmensz Nicole , Vento Anna R. , Zuber Veronica 
Published: September 2023

Importance

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent.

Objective

To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography.

Design, Setting, and Participants

The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023.

Intervention

Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group).

Main Outcomes and Measures

The primary end point of the study was distant disease–free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations.

Results

Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor–positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group.

Conclusions and Relevance

In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan.

Trial Registration

ClinicalTrials.gov Identifier: NCT02167490