Division of Breast Surgery, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
Breast Surgery Unit, San Raffaele Scientific and Research Hospital, Milan, Italy.
JAMA Oncol. 2023 Nov 1;9(11):1557-1564. doi: 10.1001/jamaoncol.2023.3759.
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.
重要性：前哨淋巴结活检（SLNB）是早期乳腺癌（BC）腋窝淋巴结分期的标准治疗方法，但由于腋窝淋巴结检查手术并非出于治愈目的，因此其必要性值得质疑。
目的：确定对于术前腋窝淋巴结超声检查结果阴性的小乳腺癌（BC）患者，省略腋窝手术是否不劣于 SLNB。
设计、设置和参与者：SOUND（前哨淋巴结与超声后观察）试验是一项在意大利、瑞士、西班牙和智利进行的前瞻性非劣效性 III 期随机临床试验。共纳入了 1463 名年龄不限、BC 最大直径达 2cm 且术前腋窝超声检查结果为阴性的患者，并于 2012 年 2 月 6 日至 2017 年 6 月 30 日期间进行了随机分组。其中 1405 名患者被纳入意向治疗分析。数据于 2022 年 10 月 10 日至 2023 年 1 月 13 日进行分析。
干预措施：符合条件的患者以 1:1 的比例随机分为接受 SLNB（SLNB 组）或不进行腋窝手术（不进行腋窝手术组）。
主要终点和措施：该研究的主要终点是 5 年的无远处疾病生存（DDFS），分析方法为意向治疗。次要终点包括远处复发累积发生率、腋窝复发累积发生率、DFS、总生存（OS）和辅助治疗建议。
结果：在 1405 名（中位数[IQR]年龄 60[52-68]岁）纳入意向治疗分析的患者中，708 名患者被随机分配至 SLNB 组，697 名患者被随机分配至不进行腋窝手术组。总体而言，中位（IQR）肿瘤大小为 1.1（0.8-1.5）cm，1234 名患者（87.8%）为雌激素受体阳性 ERBB2（前 HER2 或 HER2/neu）、非过表达 BC。在 SLNB 组中，97 名患者（13.7%）有阳性腋窝淋巴结。在 SLNB 组中，疾病评估的中位（IQR）随访时间为 5.7（5.0-6.8）年，在不进行腋窝手术组为 5.7（5.0-6.6）年。SLNB 组的 5 年远处 DDFS 为 97.7%，不进行腋窝手术组为 98.0%（对数秩 P=0.67；风险比，0.84；90%CI，0.45-1.54；非劣效性 P=0.02）。SLNB 组中观察到 12 例（1.7%）局部区域复发、13 例（1.8%）远处转移和 21 例（3.0%）死亡，不进行腋窝手术组中观察到 11 例（1.6%）局部区域复发、14 例（2.0%）远处转移和 18 例（2.6%）死亡。
结论和相关性：在这项随机临床试验中，对于术前腋窝淋巴结超声检查结果为阴性的小乳腺癌患者，省略腋窝手术不劣于 SLNB。这些结果表明，对于那些特征的患者，如果缺乏病理信息不影响术后治疗计划，则可以安全地避免任何腋窝手术。
试验注册：ClinicalTrials.gov 标识符：NCT02167490。
Cochrane Database Syst Rev. 2017-1-4
Cochrane Database Syst Rev. 2015-5-16
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