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中华乳腺病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (06) : 346 -352. doi: 10.3877/cma.j.issn.1674-0807.2022.06.003

论著

乳腺恶性叶状肿瘤预后因素分析及预后预测模型的构建
刘泰源1, 李珺1, 高济越1, 赵海东1,†()   
  1. 1. 116023　大连医科大学附属第二医院乳腺外科
  • 收稿日期:2021-04-03 出版日期:2022-12-01
  • 通信作者: 赵海东

Prognostic factor analysis and prognostic nomogram of malignant breast phyllodes tumors

Taiyuan Liu1, Jun Li1, Jiyue Gao1, Haidong Zhao1,†()   

  1. 1. Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
  • Received:2021-04-03 Published:2022-12-01
  • Corresponding author: Haidong Zhao
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引用本文：

刘泰源, 李珺, 高济越, 赵海东. 乳腺恶性叶状肿瘤预后因素分析及预后预测模型的构建[J/OL]. 中华乳腺病杂志(电子版), 2022, 16(06): 346-352.

Taiyuan Liu, Jun Li, Jiyue Gao, Haidong Zhao. Prognostic factor analysis and prognostic nomogram of malignant breast phyllodes tumors[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2022, 16(06): 346-352.

目的

探讨乳腺恶性叶状肿瘤(MPTB)的预后影响因素，并建立预后预测模型。

方法

根据纳入排除标准检索并筛选美国国立癌症研究所建立的监测、流行病学、随访结果数据库(SEER)中1 363例MPTB患者数据，采用Kaplan-Meier法计算MPTB患者的肿瘤特异性生存(CSS)，各临床病理因素对CSS的影响比较采用Log-rank检验进行单因素分析。将单因素分析有意义的变量引入Cox比例风险回归模型进行MPTB患者预后多因素分析，建立Nomogram预后预测模型并使用C-指数与校正曲线验证其预测准确性。

结果

(1)1 363例MPTB患者术后1、2、5、10年的CSS率分别为97%(1 322/1 363)、94%(1 285/1 363)、91%(1 250/1 363)和89%(1234/1 363)。(2)单因素生存分析结果显示：年龄、肿瘤直径、肿瘤分期、婚姻状态和区域淋巴结状态和MPTB患者CSS有关(χ2＝55.135、120.215、249.650 、5.230、215.208，P均<0.050)。(3)多因素分析结果显示年龄(>45岁且<68岁和≥68岁分别与≤45岁比较：HR＝2.490，95%CI：1.466~4.229，P＝0.001；HR＝5.296，95%CI：2.890~9.704，P<0.001)、肿瘤直径(>59 mm且<115 mm和≥115 mm分别与≤59 mm比较：HR＝2.187，95%CI：1.421~3.366，P＝0.002；HR＝3.846，95%CI：2.395~6.174，P<0.001)、肿瘤分期(区域和远处转移分别和局部比较：HR＝2.353，95%CI：1.409~3.929，P＝0.001；HR＝10.195，95%CI：5.187~20.038，P<0.001)和区域淋巴结阳性(HR＝4.830，95%CI：1.883~12.387，P＝0.001)均是MPTB患者预后的独立影响因素。(4)利用年龄、肿瘤直径、肿瘤分期和区域淋巴结状态这4个变量建立了Nomogram预后预测模型，该模型的C指数＝0.82，并且通过校正曲线证明了模型具有良好的预测能力。

结论

高龄、大肿瘤、局部进展及转移的MPTB患者预后不佳，早期发现和早期治疗对MPTB患者非常重要。

关键词: 叶状肿瘤, 预后, 危险因素
Objective

To investigate the prognostic factors in patients with malignant phyllodes tumors of the breast (MPTB), and establish a predictive nomogram.

Methods

In accordance with the inclusive and exclusive criteria, the data of 1 363 patients diagnosed with MPTB in the Surveillance, Epidemiology and Results (SEER) database of the U. S. National Cancer Institute were analyzed in this study. The Kaplan-Meier survival analyses were performed to evaluate the cause-specific survival (CSS) of MPTB patients. The log-rank test was used to explore the relationship between clinicopathological characteristics and CSS. Multivariate analysis by Cox proportional hazards regression model was performed to analyze the prognostic factors from the variables with a significant difference in univariate analysis. The nomogram was developed to predict the CSS of the MPTB. The C-index and calibration plots were generated to evaluate the accuracy of the nomogram.

Results

(1) The 1-year, 2-year, 5-year, and 10-year CSS of 1 363 patients were 97%(1322/1 363), 94%(1 285/1 363), 91%(1250/1 363), and 89%(1 234/1 363), respectively. (2) Univariate analysis found that age, tumor size, tumor stage, marital status, and regional lymph node status were related to CSS of MPTB patients(χ2=55.135, 120.215, 249.650, 5.230, 215.208, all P<0.050). (3)Multivariate analysis showed that the independent factors for the prognosis of MPTB patients were as follow: age (≤45 years vs 45-68 years: HR=2.490, 95%CI: 1.466-4.229, P=0.001; ≤45 years vs ≥68 years: HR=5.296, 95%CI: 2.890-9.704, P<0.001), tumor size(≤59 mm vs 59-115 mm: HR=2.187, 95%CI: 1.421-3.366, P=0.002; ≤59 mm vs ≥115 mm: HR=3.846, 95%CI: 2.395-6.174, P<0.001), tumor stage (local vs regional: HR=2.353, 95%CI: 1.409-3.929, P=0.001; local vs distant metastasis: HR=10.195, 95%CI: 5.187-20.038, P<0.001) and positive regional lymph node (HR=4.830, 95%CI: 1.883-12.387, P=0.001). (4) The four factors (age, tumor size, tumor stage and regional lymph node status) were used to generate a nomogram predicting the CSS of patients diagnosed with MPTB. The C-index was 0.82. The calibration plots showed a good predictive ability of the model.

Conclusion

MPTB patients at advanced age or with large tumors, local progression and metastasis have a poor prognosis, and early detection and treatment is important for MPTB patients.

Key words: Phyllodes tumors, Prognosis, Risk factor
表1 乳腺恶性叶状肿瘤预后因素的变量赋值表
临床病理因素 变量 分类赋值
年龄 X1 ≤45岁＝1；>45岁且<68岁＝2；≥68岁＝3
肿瘤直径 X2 ≤59 mm＝1；>59 mm且<115 mm＝2；≥115 mm＝3
肿瘤分期 X3 局部＝1；区域＝2；远处转移＝3
种族 X4 白人＝1；黑人＝2；亚洲人及太平洋岛国人＝3；美国印第安人＝4；拉丁美洲人＝5
婚姻状态 X5 已婚＝1；其他婚姻状态＝2
肿瘤位侧 X6 左侧＝1；右侧＝2
肿瘤位置 X7 乳头＝1；乳房中央区＝2；内上象限＝3；内下象限＝4；外上象限＝5；外下象限＝6；跨象限＝7
化疗情况 X8 未化疗/未知＝0；化疗＝1
放射治疗情况 X9 未放射治疗＝0；放射治疗＝1
手术方式 X10 保留乳房手术＝1；更大范围手术＝2
区域淋巴结状态 X11 阴性＝0；阳性＝1；未评估＝2
生存情况 Y 生存＝0；肿瘤特异性死亡＝1
图1 1 363例乳腺恶性叶状肿瘤患者的生存曲线　a图为所有患者的肿瘤特异性生存曲线；b图为不同年龄患者的肿瘤特异性生存曲线(χ2＝55.135, P<0.001); c图为不同肿瘤直径患者的肿瘤特异性生存曲线(χ2＝120.215, P<0.001); d图为不同肿瘤分期患者的肿瘤特异性生存曲线(χ2＝249.650, P<0.001); e图为不同婚姻状态患者的肿瘤特异性生存曲线(χ2＝5.230，P＝0.022); f图为不同区域淋巴结状态患者的肿瘤特异性生存曲线(χ2＝215.208, P<0.001)
表2 1 363例乳腺恶性叶状肿瘤患者预后影响因素的单因素分析
临床病理特征 例数(%) χ2值 P值
年龄      
  ≤45岁 463(34.0) 55.135 <0.001
  >45岁且<68岁 751(55.1)
  ≥68岁 149(10.9)
肿瘤直径      
  ≤59 mm 896(65.7) 120.215 <0.001
  >59 mm且<115 mm 314(23.1)
  ≥115 mm 153(11.2)
肿瘤分期      
  局部 1 268(93.0) 249.650 <0.001
  区域 78(5.7)
  远处转移 17(1.3)
种族      
  白人 780(57.2) 5.195 0.268
  黑人 147(10.8)
  亚洲人及太平洋岛国人 184(13.5)
  美国印第安人 7(0.5)
  拉丁美洲人 245(18.0)
婚姻状态      
  已婚 800(58.7) 5.230 0.022
  其他婚姻状态 563(41.3)
肿瘤位侧      
  左 670(49.2) 0.776 0.378
  右 693(50.8)
肿瘤位置      
  乳头 13(1.0) 11.475 0.075
  乳房中央区 109(8.0)
  内上象限 144(10.6)
  内下象限 51(3.7)
  外上象限 479(35.1)
  外下象限 114(8.4)
  跨象限 453(33.2)
放射治疗a      
  未接受放射治疗 214(15.7) 0.273 0.601
  接受放射治疗 1 149(84.3)
化疗b      
  未接受化疗 46(3.4) 0.714 0.398
  接受化疗 1 317(96.6)
手术范围c      
  保留乳房手术 759(55.7) 0.457 0.499
  乳房切除术及更大范围手术 604(44.3)
区域淋巴结状态      
  阴性 337(24.7) 215.208 <0.001
  阳性 7(0.5)
  未评估 1 019(74.8)
表3 1 363例乳腺恶性叶状肿瘤患者预后影响的多因素Cox比例风险回归分析
因素 β值 标准误 Wald值 风险比 95%置信区间 P值
年龄            
  ≤45岁(参照) － － － － － －
  >45岁且<68岁 0.912 0.270 11.402 2.490 1.466~4.229 0.001
  ≥68岁 1.667 0.309 29.092 5.296 2.890~9.704 <0.001
肿瘤直径            
  ≤59 mm(参照) － － － － － －
  >59 mm且<115 mm 0.783 0.220 12.650 2.187 1.421~3.366 <0.001
  ≥115 mm 1.347 0.242 31.093 3.846 2.395~6.174 <0.001
肿瘤分期            
  局部(参照) － － － － － －
  区域 0.856 0.262 10.707 2.353 1.409~3.929 0.001
  远处转移 2.322 0.345 45.346 10.195 5.187~20.038 <0.001
  区域淋巴结阳性 1.575 0.481 10.741 4.830 1.883~12.387 0.001
图2 1 363例乳腺恶性叶状肿瘤预后预测模型的列线图注：CSS为肿瘤特异性生存率
图3 乳腺恶性叶状肿瘤患者预后预测模型的肿瘤特异性生存校正曲线　a、b、c图分别为2年、3年、5年的肿瘤特异性生存校正曲线注：CSS为肿瘤特异性生存；在一个理想的预测模型中，预测值等于真实值，曲线则刚好落在45度的对角线上，当校准曲线在对角线之上时，则预测值大于真实值，当校准曲线在对角线之下时，则预测值小于真实值
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