基于临床及病理参数构建并验证预测乳腺浸润性导管癌淋巴结转移的风险模型

Construction and validation of a risk model for predicting lymph node metastasis of breast infiltrating duct carcinoma based on clinical and pathological parameters

目的分析乳腺浸润性导管癌重要的临床及病理参数,构建并验证列线图,非创伤性地预测其发生淋巴结转移的风险概率。方法从SEER数据库收集2011年至2014年诊断为乳腺浸润性导管癌患者的临床及病理资料,共纳入155510例患者,按7∶3随机分训练队列和内部验证队列。收集江苏大学附属句容医院2015-2019年确诊的50例乳腺浸润性导管癌患者纳入外部验证队列。对训练队列的临床及病理参数进行单因素和多因素Logistic回归分析,得到预测淋巴结转移的独立危险因素并构建列线图模型。列线图中,将患者的独立危险因素各项评分汇总得到总分,总分越高,说明其发生区域淋巴结转移概率越高。受试者工作曲线下面积(AUC)评估列线图的预测能力,校准图评估列线图的准确性,分别进行内外部验证。结果训练队列108893例,内部验证队列46617例,外部验证队列50例。对训练队列的Logistic回归分析中,发现疾病诊断年龄、性别、肿瘤大小、组织学分级及分子分型是乳腺浸润性导管癌淋巴结转移的独立危险因素(P<0.001),这5个因素都包括在列线图中。列线图总分为200分,其中肿瘤大小是淋巴结转移最危险因素。患者越年轻、组织学分级越高、肿瘤体积越大且分子分型是HER-2过表达型,总分越高,越容易发生区域淋巴结转移。在训练队列中,列线图表现出稳健的辨别力,AUC值为0.749;内外部验证队列中,AUC值分别为0.738和0.720,提示对淋巴结转移风险预测具有良好的预测价值。校准曲线显示列线图预测的淋巴结转移风险概率与实际概率之间较好的一致性。结论由疾病诊断年龄、性别、肿瘤大小、组织学分级及分子分型5个独立危险因素构建的列线图,能够非创伤性地个体化地预测乳腺浸润性导管癌患者淋巴结转移的风险概率,为临床治疗提供理论依据。

Objective To analyze importantclinical and pathological parameters of infiltrating duct carcinoma of the breast and to construct and validate a nomogram that is non traumatic in predicting the risk probability of developing lymph node metastasis.Methods Clinical and pathological data of patients diagnosed with primary breast infiltrative ductal carcinoma from 2011 to 2014 were collected from the Surveillance,Epidemiology,and End Results(SEER)database.A total of 155510 patients were included and randomly divided into a training cohort and an internal verification cohort at a ratio of 7∶3.Fifty patients diagnosed with primary breast infiltrative ductal carcinoma in Jurong Hospital Affiliated to Jiangsu University from 2015 to 2019 were included in the external validation cohort.Univariate and multivariate logistic regression analyses of clinical and pathological parameters were performed to obtain independent risk factors for predicting lymph node metastasis and construct a nomogram.In the nomogram,each score of the independent risk factors of the patients was pooled to obtain a total score of the model,and a higher total score indicated a higher probability of developing lymph node metastasis.C-index,AUC were used to evaluate the predictive ability of the nomogram.Calibration plots were performed to assess nomogram accuracy.Results In total,108893 patients were included in the training cohort,46617 patients were included in the internal validation cohort,and 50 patients were included in the external validation cohort.On logistic regression analysis of the training cohort,age at disease diagnosis,gender,tumor size,histological grade and molecular classification were found to be independent risk factors for lymph node metastasis(P<0.001),and five factors were included in the nomogram.The total score of the nomogram was 200 points,in which tumor size was the key risk factor for lymph node metastasis.The younger patients wtih a higher grade,a larger tumor volume and HER-2-overexpressing type were shown a higher total score,and indicated a higher possibility of the regional lymph node metastasis.In the training cohort,the nomogram showed robust discrimination with the area under the curve(AUC)of 0.749.In the internal and external validation cohorts,AUC were 0.738 and 0.720,respectively,showing a good predictive value for lymph node metastasis risk prediction.The calibration curve showed the best agreement between the nomogram predicted probability of lymph node metastasis risk and the actual probability.Conclusion In this study,a nomogram constructed by five independent risk factors,such as age,sex,tumor size,histological grade and molecular classification of tumor,can predict the risk probability of lymph node metastasis in patients with infiltrating duct carcinoma of breast in a noninvasive and individualized way,and provide theoretical basis for clinical treatment.