Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes

Abstract

ImportanceSentinel 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.ObjectiveTo 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 ParticipantsThe 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.InterventionEligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group).Main Outcomes and MeasuresThe 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.ResultsAmong 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT02167490

The SOUND Randomized Clinical Trial Results—Reply

“…It will take some time before axillary surgery will be abandoned, but data from the SOUND trial provide information useful for treating many patients with early breast cancer as well as patients with ductal carcinoma in situ. In fact, women with intraductal lesions undergoing limited surgery should be spared SLNB and, in the case where an invasive component is found in the final pathologic report, data from this trial provide robust information supporting the omission of an additional operation to remove the SLNB in most patients.…”

“…Patients who participated in the SOUND trial could be considered at low risk for recurrence in the short term. In fact, due to the inclusion criteria, postmenopausal women with small ER-positive ERBB2 -negative breast cancer made up most of the participants, but this subset also represents the greatest number of patients with early breast cancer, at least in countries where screening programs are available and effective.…”

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“…With median followup of 5.8 years, distant DFS was 97.7% in the SLND arm and 98.0% in the observation arm (HR 0.84 (90% CI 0.45−1.54), p = 0.024). 24 Despite a 13.7% incidence of axillary lymph node involvement in the SLND arm, the cumulative incidence of clinical axillary lymph node recurrence was only 0.4% at 5 years. Only 7 of the 21 deaths in the SLND arm were from breast cancer, compared with 4 of the 18 deaths in the observation arm.…”

The SOUND Randomized Clinical Trial Results

“…To the Editor We read with great interest the article by Gentilini and colleagues . The de-escalation of axillary management has evolved from axillary clearance to sentinel lymph node biopsy (SLNB) and further to omission of axillary management even in the presence of 1 to 2 positive sentinel lymph nodes in patients with early breast cancer who undergo breast conservation therapy, which has in turn led to questioning of the role of SLNB in this subset of patients and the concept of noninvasive sonological staging of the axilla.…”