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. 2023 Nov 1;9(11):1557-1564.
doi: 10.1001/jamaoncol.2023.3759.

Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial

Oreste Davide Gentilini  1   2 , Edoardo Botteri  3   4 , Claudia Sangalli  5 , Viviana Galimberti  1 , Mauro Porpiglia  6 , Roberto Agresti  7 , Alberto Luini  1 , Giuseppe Viale  8   9 , Enrico Cassano  10 , Nickolas Peradze  1 , Antonio Toesca  1 , Giulia Massari  1 , Virgilio Sacchini  1   9 , Elisabetta Munzone  11 , Maria Cristina Leonardi  12 , Francesca Cattadori  13 , Rosa Di Micco  2 , Emanuela Esposito  14 , Adele Sgarella  15 , Silvia Cattaneo  16 , Massimo Busani  17 , Massimo Dessena  18 , Anna Bianchi  19 , Elisabetta Cretella  20 , Francisco Ripoll Orts  21 , Michael Mueller  22 , Corrado Tinterri  23   24 , Badir Jorge Chahuan Manzur  25 , Chiara Benedetto  6 , Paolo Veronesi  1   9 ; SOUND Trial Group
Collaborators, Affiliations

Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial

Oreste Davide Gentilini et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gentilini reported receiving personal fees from AstraZeneca, Bayer, BD, Eli Lilly and Company, and MSD outside the submitted work. Dr Viale reported receiving personal fees from AstraZeneca, Daiichi Sankyo Company, Eli Lilly and Company, MSD, Pfizer, and Roche outside the submitted work. Dr Munzone reported receiving personal fees from AstraZeneca, Daiichi Sankyo Company, Exact Sciences Corporation, Ipsen Pharma, MSD Oncology, Pfizer, and Seagen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram
BC indicates breast cancer; DIN, ductal intraepithelial neoplasia; ITT, intention to treat; LIN, lobular intraepithelial neoplasia; and SLNB, sentinel lymph node biopsy.
Figure 2.
Figure 2.. Kaplan-Meier Estimates of Distant Disease–Free Survival, Disease-Free Survival, and Overall Survival
SLNB indicates sentinel lymph node biopsy.
See this image and copyright information in PMC

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