基于预测的高淋巴结负荷风险模型：针对阳性哨兵淋巴结（SLN）乳腺癌患者的临床应用

在临床上，伴有1或2个哨兵淋巴结（SLN）宏转移的无淋巴结转移（cN0）乳腺癌患者，常采用省略完成腋窝淋巴结清扫（CALND）的策略。高淋巴结负荷（≥4个腋窝淋巴结转移）是ERBB2阴性乳腺癌加大治疗强度的指征，因此避免CALND可能导致治疗不足。本研究旨在建立一套预测ERBB2阴性乳腺癌（包括所有组织学类型和腺叶型乳腺癌）中高淋巴结负荷的模型，排除进行CALND的患者。此项前瞻性试验“乳腺癌哨兵淋巴结活检：宏转移后省略腋窝清扫（SENOMAC）”于2015年1月至2021年12月在五个欧洲国家随机将患者1:1分为接受或省略CALND组，纳入年龄≥18岁的cN0 T1-T3期乳腺癌伴1-2个SLN宏转移的患者。数据随机分为训练集（80%）和测试集（20%），两个集中的高负荷比例相当。通过多变量逻辑回归建立预测模型，构建列线图。仅对接受CALND的ERBB2阴性腔隙型乳腺癌患者进行分析。2023年6月至2024年4月进行数据分析。预测高淋巴结负荷的预测指标包括SLN宏转移数、微转移存在、SLN比率、SLN外包膜扩展及肿瘤大小（腺叶型不包括在内）。在验证集中（n=201）模型的AUC为0.74（95%CI：0.62-0.85），校准良好。在灵敏度≥80%的阈值下，除5名低风险患者外，其他均正确分类，阴性预测值达94%。腺叶型乳腺癌的模型AUC为0.74（95%CI：0.66-0.83）。该预测模型和列线图有助于制定系统性治疗方案，避免因CALND引起的臂部并发症。需要进一步的外部验证。临床试验注册号：NCT02240472。

In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment.To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND.The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024.Predictors of high nodal burden.High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration.Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83).The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed.ClinicalTrials.gov Identifier: NCT02240472.