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浙江大学学报(医学版)  2021, Vol. 50 Issue (1): 81-89    DOI: 10.3724/zdxbyxb-2021-0013
原著     
T1期乳腺癌患者发生同侧腋窝淋巴结转移风险列线图的建立
付媛媛1,2(),姜晶鑫1,陈述政2,邱福铭1,*()
1. 浙江大学医学院附属第二医院肿瘤内科,浙江 杭州 310009
2. 浙江大学丽水医院乳腺外科,浙江 丽水 323000
Establishment of risk prediction nomogram for ipsilateral axillary lymph node metastasis in T1 breast cancer
FU Yuanyuan1,2(),JIANG Jingxin1,CHEN Shuzheng2,QIU Fuming1,*()
1. Department of Medical Oncology,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China;
2. Department of Breast Surgery,Zhejiang University Lishui Hospital,Lishui 323000,Zhejiang Province,China
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摘要:

目的:建立T1期(原发肿瘤最大直径 2?cm及以下)乳腺癌患者发生同侧腋窝淋巴结转移风险的列线图。 方法:收集2010年1月至2015年6月在浙江大学医学院附属第二医院及浙江大学丽水医院接受手术治疗的T1期乳腺癌患者的临床病理资料。共入组907例患者,其中浙江大学医学院附属第二医院患者作为建模组( n=573),浙江大学丽水医院患者作为验证组( n=334)。运用单因素Logistic回归分析风险因素,多因素Logistic回归进一步筛选独立影响因素,利用影响因素建立预测T1期乳腺癌患者同侧腋窝淋巴结转移风险的列线图。运用C指数、受试者操作特征曲线、校准曲线以及临床决策曲线分析模型的校准度、预测能力和临床效益。 结果:单因素分析结果显示,T1期乳腺癌患者发生同侧腋窝淋巴结转移与原发肿瘤大小、脉管癌栓、Ki-67、组织病理学分级和分子分型相关( P<0.05或 P<0.01)。多因素Logistic回归分析显示,T1期乳腺癌患者发生同侧腋窝淋巴结转移的独立影响因素为原发肿瘤大于0.5 cm、有脉管癌栓、Ki-67阳性、雌激素受体(ER)阳性以及组织病理学分级2~3级( P<0.05或 P<0.01)。基于上述5个独立影响因素构建列线图预测模型,建模组和验证组C指数分别为0.739(95% CI:0.693~0.785)和0.736(95% CI:0.678~0.793),模型预测能力良好。建模组和验证组校正曲线、临床决策曲线提示模型一致性和临床获益良好。 结论:原发肿瘤大小、组织病理学分级、脉管癌栓、Ki-67和ER状态是T1期乳腺癌患者发生同侧腋窝淋巴结转移的重要预测因素。建立的风险预测列线图可以有效预测患者发生同侧腋窝淋巴结转移的风险,为临床医生制订个体化的腋窝管理方案提供参考。

关键词: 乳腺肿瘤淋巴转移危险因素列线图预测    
Abstract:

Objective:To establish and verify a risk prediction nomogram for ipsilateral axillary lymph node metastasis in breast cancer stage T1 (mass ≤ 2 cm). Methods:The clinicopathological data of 907 patients with T1 breast cancer who underwent surgical treatment from January 2010 to June 2015 were collected,including 573 cases from the Second Affiliated Hospital of Zhejiang University School of Medicine (modeling group) and 334 cases from Zhejiang University Lishui Hospital (verification group). The risk factors of ipsilateral axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression. The influencing factors were used to establish a nomogram for predicting ipsilateral axillary lymph nodes metastasis in T1 breast cancer. The model calibration,predictive ability and clinical benefit in the modeling group and the verification group were analyzed by C index,receiver operating characteristic curve,calibration curve and decision curve analysis (DCA) curve,respectively. Results:Univariate analysis showed that lymph node metastasis was related with primary tumor size,vascular tumor thrombus,Ki-67,histopathological grade,and molecular type ( P<0.05 or P<0.01). Multivariate logistic regression analysis showed that the primary tumor > 0.5?cm, vascular tumor thrombus,Ki-67 positive,estrogen receptor (ER) positive,and histopathological grade 2-3 were independent risk factors of axillary lymph node metastasis ( P<0.05 or P<0.01). Based on the independent risk factors,a nomogram prediction model was established. The C indexes of the model group and the validation group were 0.739 (95% CI:0.693-0.785) and 0.736 (95% CI:0.678-0.793),respectively. The calibration curve and DCA curve of the modeling group and the verification group indicated that the model was consistent and had good clinical benefit. Conclusions:Primary tumor size,histopathological grade,vascular tumor thrombus,Ki-67,and ER status are predictors of ipsilateral axillary lymph node metastasis in T1 breast cancer. The established prediction nomogram can effectively predict the risk of ipsilateral axillary lymph node metastasis in T1 breast cancer,which can be used as a reference for individualized axillary management.

Key words: Breast neoplasm    Lymphatic metastasis    Risk factors    Nomogram    Prediction
收稿日期: 2020-11-30 出版日期: 2021-05-16
CLC:  R730.4  
基金资助: 国家自然科学基金(81672802); 浙江省自然科学基金(LZ17H160004)
通讯作者: 邱福铭     E-mail: zjdrfu@163.com;zdf2zlk@163.com
作者简介: 付媛媛,主治医师,主要从事乳腺癌临床研究;E-mail:zjdrfu@163.com;https://orcid.org/0000-0001-6144-4789
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引用本文:

付媛媛,姜晶鑫,陈述政,邱福铭. T1期乳腺癌患者发生同侧腋窝淋巴结转移风险列线图的建立[J]. 浙江大学学报(医学版), 2021, 50(1): 81-89.

FU Yuanyuan,JIANG Jingxin,CHEN Shuzheng,QIU Fuming. Establishment of risk prediction nomogram for ipsilateral axillary lymph node metastasis in T1 breast cancer. J Zhejiang Univ (Med Sci), 2021, 50(1): 81-89.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0013        http://www.zjujournals.com/med/CN/Y2021/V50/I1/81

图 1  研究对象筛选流程图

组别

n

年龄≥50岁 *

淋巴结转移

T分期

有脉管癌栓

有导管原位癌成分

ER阳性

PR阳性

Her-2阳性

T1a

T1b

T1c

建模组

573

319(55.7)

141(24.6)

47(8.2)

114(19.9)

412(71.9)

44(7.7)

174(30.4)

408(71.2)

357(62.3)

134(23.4)

验证组

334

175(52.5)

97(29.0)

31(9.3)

44(13.2)

259(77.5)

35(10.5)

44(13.2)

263(78.7)

236(70.7)

79(23.7)

t/ χ 2

5.509

249.161

6.666

2.081

34.161

6.229

6.508

0.008

P

<0.05

<0.01

<0.05

0.149

<0.01

<0.05

<0.05

0.927

组别

n

Ki-67阳性

组织病理学分级

分子分型

1级

2级

3级

未分级

Luminal A型

LuminalB型(Her-2阴性)

LuminalB型(Her-2阳性)

Her-2过表达型

三阴性乳腺癌

建模组

573

279(48.7)

110(19.2)

312(54.5)

124(21.6)

27(4.7)

229(40.0)

123(21.5)

68(11.9)

66(11.5)

87(15.2)

验证组

334

204(61.1)

44(13.2)

145(43.3)

122(36.5)

23(6.9)

114(34.1)

104(31.1)

47(14.1)

32(9.6)

37(11.1)

t/ χ 2

13.005

28.660

13.928

P

<0.01

<0.01

<0.01

表 1  建模组与验证组临床和病理基线特征比较
图 2  建模组T1期乳腺癌患者部分临床病理特征与腋窝淋巴结转移关系的多因素分析结果

影响因素

OR(95% CI

P

年龄

0.843(0.576~1.234)

>0.05

原发肿瘤大小(T分期)

?

?

T1b

4.787(1.072~21.377)

<0.05

T1c

0.138(2.182~38.274)

<0.01

导管原位癌成分

0.803(0.526~1.227)

>0.05

脉管癌栓

6.442(3.368~12.322)

<0.01

ER阳性

1.242(0.807~1.911)

>0.05

PR阳性

0.929(0.629~1.373)

>0.05

Her-2阳性

1.356(0.879~2.093)

>0.05

Ki-67阳性

2.269(1.532~3.360)

<0.01

分子分型

?

?

LuminalB型(Her-2阴性)

2.325(1.414~3.823)

<0.01

LuminalB型(Her-2阳性)

1.802(0.971~3.344)

>0.05

Her-2过表达型

1.749(0.934~3.275)

>0.05

三阴性乳腺癌

0.975(0.516~1.841)

>0.05

组织病理学分级

?

?

2级

3.391(1.687~6.816)

<0.01

3级

6.316(3.002~13.287)

<0.01

未分级

1.739(0.501~6.040)

>0.05

表 2  建模组T1期乳腺癌临床病理特征与腋窝淋巴结转移关系的单因素分析结果
图 3  T1期乳腺癌患者发生同侧腋窝淋巴结转移的风险列线图
图 4  T1期乳腺癌患者发生同侧腋窝淋巴结转移风险预测模型的ROC曲线
图 5  T1期乳腺癌患者发生同侧腋窝淋巴结转移风险预测模型的校准曲线
图 6  T1期乳腺癌患者发生同侧腋窝淋巴结转移风险预测模型的临床决策曲线
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