ImportanceIn 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.ObjectiveTo develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND.Design, Setting, and ParticipantsThe 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.ExposurePredictors of high nodal burden.Main Outcomes and MeasuresHigh nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration.ResultsOf 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).Conclusions and RelevanceThe 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.Trial RegistrationClinicalTrials.gov Identifier: NCT02240472

中文翻译：

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预测前哨淋巴结阳性管腔 ERBB2 阴性乳腺癌患者高淋巴结负荷


重要性对于临床淋巴结阴性 （cN0） 乳腺癌和 1 或 2 个前哨淋巴结 （SLN） 大转移的患者，省略完成腋窝淋巴结清扫术 （CALND） 是标准配置。高淋巴结负荷 （≥4 腋窝淋巴结转移） 是管腔乳腺癌强化治疗的适应证;因此，放弃 CALND 可能会导致治疗不足。目的开发无 CALND.Design、环境和参与者的管腔 ERBB2 阴性乳腺癌（所有组织学类型和小叶乳腺癌）高淋巴结负荷预测模型乳腺癌前瞻性前哨淋巴结活检：大转移后省略腋窝清除 （SENOMAC） 试验将 2015年1月至 2021 年 12 月在 cN0 T1-T3 乳腺癌成年患者和 1 或 2 个 SLN 大转移患者中以 1：1 的比例随机分配至 CALND 或其遗漏遍布 5 个欧洲国家。该队列被随机分为训练组 （80%） 和测试组 （20%），高淋巴结负荷的比例相等。预测模型是通过多变量 logistic 回归在完整的管腔 ERBB2 阴性队列和小叶乳腺癌亚组中开发的。构建了列线图。本诊断/预后研究介绍了 SENOMAC 试验的预先指定的二次分析的结果。在此，仅选择分配给 CALND 的管腔 ERBB2 阴性肿瘤患者。本文的数据分析于 2023 年 6 月至 2024 年 4 月进行。主要结局和测量高淋巴结负荷定义为 ≥4 个腋窝淋巴结转移。对管腔预测模型进行了区分和校准评估。结果1010 例患者 （中位 [范围] 年龄，61 [34-90] 岁;1006 例 [99.6%] 女性和 4 例 [0.4%] 男性），138 例 （13.7%） 淋巴结负荷高，212 例 （21.0%） 患有小叶乳腺癌。训练集中的模型 （n = 804） 包括 SLN 大转移的数量、 SLN 微转移的存在、 SLN 比率、 SLN 包膜外扩展的存在和肿瘤大小 （不包括在小叶亚组中）。在测试集 （n = 201） 中验证后，受试者工作特征曲线下面积 （AUC） 为 0.74 （95% CI，0.62-0.85），校准令人满意。在 ≥80% 的敏感性阈值下，除 5 名低风险患者外，所有患者均被正确分类，对应的阴性预测值为 94%。小叶亚组的预测模型达到 0.74 （95% CI，0.66-0.83）。结论和相关性预测模型和列线图可能有助于全身治疗决策，而不会使患者面临因 CALND 导致手臂发病的风险。需要外部验证。试验注册临床试验。gov 标识符： NCT02240472