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中华乳腺病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (04) : 213 -220. doi: 10.3877/cma.j.issn.1674-0807.2020.04.004

所属专题： 总编推荐； 文献；

论著

纤维蛋白原/白蛋白比值比对可手术乳腺癌患者预后的影响
曹希1, 周易冬1, 茅枫1, 林燕1, 黄欣1, 孙强1,†()   
  1. 1. 100032　中国医学科学院北京协和医院乳腺外科
  • 收稿日期:2018-11-30 出版日期:2020-08-01
  • 通信作者: 孙强
  • 基金资助:
    北京市科技计划项目资助(D161100000816005)

Effect of fibrinogen to albumin ratio on prognosis of operable breast cancer patients

Xi Cao1, Yidong Zhou1, Feng Mao1, Yan Lin1, Xin Huang1, Qiang Sun1,†()   

  1. 1. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100032, China
  • Received:2018-11-30 Published:2020-08-01
  • Corresponding author: Qiang Sun
  • About author:
    Corresponding author: Sun Qiang, Email:
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引用本文：

曹希, 周易冬, 茅枫, 林燕, 黄欣, 孙强. 纤维蛋白原/白蛋白比值比对可手术乳腺癌患者预后的影响[J/OL]. 中华乳腺病杂志(电子版), 2020, 14(04): 213-220.

Xi Cao, Yidong Zhou, Feng Mao, Yan Lin, Xin Huang, Qiang Sun. Effect of fibrinogen to albumin ratio on prognosis of operable breast cancer patients[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2020, 14(04): 213-220.

目的

探讨纤维蛋白原/白蛋白比值比(FAR)对可手术乳腺癌患者预后的影响。

方法

依据纳入、排除标准，收集中国医学科学院北京协和医院2013年1～12月收治的520例Ⅰ～Ⅲ期可手术乳腺癌患者临床资料进行回顾性研究。在术前检测血浆纤维蛋白原和白蛋白水平。将纤维蛋白原与白蛋白质量浓度比值乘以100定义为FAR。根据受试者工作特征曲线确定FAR最佳临界值，并依据最佳临界值将受试者分为高FAR组(FAR>6.99)147例和低FAR组(FAR≤6.99)343例。采用Kaplan-Meier法和log-rank检验评估2组患者的DFS和OS，用Cox比例风险回归模型分析患者DFS和OS的影响因素。

结果

log-rank检验显示，高FAR组患者的DFS和OS均比低FAR组差(χ2＝32.885、16.320，P均<0.001)。Cox比例风险回归模型单因素分析和多因素分析均显示：高FAR为患者DFS的独立危险因素(HR＝4.092，95%CI：2.425～6.903，P<0.001；HR＝4.226，95%CI：2.476～7.212，P<0.001);高FAR为患者OS的独立危险因素(HR＝3.907，95%CI：1.913～7.978，P<0.001；HR＝4.320，95%CI：2.087～8.942，P<0.001)。

结论

术前高FAR患者的无疾病进展时间更短，OS率更低。术前FAR水平有望成为预测乳腺癌患者预后的有效指标。

关键词: 乳腺肿瘤, 纤维蛋白原, 白蛋白, 预后, 生存分析
Objective

To investigate the effect of preoperative fibrinogen to albumin ratio(FAR)on prognosis of operable breast cancer patients.

Methods

According to the inclusion and exclusion criteria, 520 patients with stage Ⅰ to Ⅲ operable breast cancer in the Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from January to December 2013 were involved in this retrospective study. Serum levels of fibrinogen and albumin were measured before operation. FAR was defined as the concentration ratio of fibrinogen and albumin multiplied by 100. Subjects were divided into two groups according to the cutoff value determined by the receiver operating characteristic curve: high FAR group(FAR>6.99)(147 patients)and low FAR group(FAR≤6.99)(343 patients). DFS and OS in two groups were assessed using the Kaplan-Meier method and log-rank test. Cox proportional hazard regression model was used to identify the influencing factors of DFS and OS.

Results

The log-rank test showed that high FAR group had significantly lower DFS and OS compared with low FAR group (χ2=32.885, 16.320, both P<0.001). The univariate and multivariate analyses showed that high FAR was an independent risk factor of DFS (HR=4.092, 95%CI: 2.425-6.903, P<0.001; HR=4.226, 95%CI: 2.476-7.212, P<0.001)and OS (HR=3.907, 95%CI: 1.913-7.978, P<0.001; HR=4.320, 95%CI: 2.087-8.942, P<0.001).

Conclusion

The patients with preoperative high FAR are prone to short progression-free survival and low OS rate, so preoperative FAR is a potential prognostic factor of breast cancer.

Key words: Breast neoplasms, Fibrinogen, Serum albumin, Prognosis, Survival analysis
图1 纤维蛋白原/白蛋白比值比预测乳腺癌患者无瘤生存的受试者工作特征曲线
图2 纤维蛋白原/白蛋白比值比预测乳腺癌患者总生存的受试者工作特征曲线
表1 乳腺癌患者DFS和OS影响因素的Cox比例风险回归模型变量赋值表
变量 变量类型 变量分类及赋值
FAR X1 低FAR组＝0，高FAR组＝1
腋窝淋巴结状态 X2 阴性＝0，阳性＝1
TNM分期 X3 Ⅰ期＝0，Ⅱ＋Ⅲ期＝1
肿瘤直径 X4 ≤2 cm＝0，>2 cm＝1
Ki67 X5 ≤14%＝0，>14%＝1
脉管癌栓 X6 无＝0，有＝1
年龄 X7 ≤50岁＝0，>50岁＝1
激素受体 X8 阳性＝0，阴性＝1
HER-2 X9 阴性＝0，阳性＝1
组织学分级 X10 1、2级＝0，3级＝1
DFS Y1 无复发转移＝0，有复发转移＝1
OS Y2 存活＝0，死亡＝1
表2 2组乳腺癌患者临床病理因素比较[例(%)]
临床病理因素 低FAR组(n＝373) 高FAR组(n＝147) χ2值 P值
年龄        
  ≤50岁 232(62.2) 56(38.1) 24.791 <0.001
  >50岁 141(37.8) 91(61.9)    
肿瘤直径        
  ≤2 cm 194(52.0) 82(55.8) 0.602 0.438
  >2 cm 179(48.0) 65(44.2)    
腋窝淋巴结转移        
  无 230(61.7) 84(57.1) 0.900 0.343
  有 143(38.3) 63(42.9)    
TNM分期        
  Ⅰ期 152(40.8) 63(42.9) 0.193 0.660
  Ⅱ、Ⅲ期 221(59.2) 84(57.1)    
激素受体        
  阳性 290(77.7) 110(74.8) 0.506 0.477
  阴性 83(22.3) 37(25.2)    
HER-2        
  阴性 278(74.5) 119(81.0) 2.408 0.121
  阳性 95(25.5) 28(19.0)    
组织学分级        
  1、2级 273(73.2) 115(78.2) 1.415 0.234
  3级 100(26.8) 32(21.8)    
脉管癌栓        
  无 273(73.2) 106(72.1) 0.062 0.803
  有 100(26.8) 41(27.9)    
Ki67        
  ≤14% 163(43.7) 62(42.2) 0.100 0.752
  >14% 210(56.3) 85(57.8)    
图3 高FAR组与低FAR组乳腺癌患者的生存曲线　a图为患者无瘤生存曲线；b图为患者总生存曲线
图4 不同分子分型乳腺癌中高FAR组与低FAR组患者无瘤生存曲线比较　a～d图分别为luminal A型、luminal B型、HER-2过表达型和三阴性乳腺癌中高FAR组与低FAR组患者的无瘤生存曲线
图5 不同分子分型乳腺癌中高FAR组与低FAR组患者总生存曲线比较　a～d图分别为luminal A型、luminal B型、HER-2过表达型和三阴性乳腺癌中高FAR组与低FAR组患者的总生存曲线
表3 影响乳腺癌患者无瘤生存的单因素分析(n＝520)
临床病理因素 回归系数 标准误 Wald值 风险比 95%置信区间 P值
FAR 1.409 0.267 27.883 4.092 2.425～6.903 <0.001
淋巴结 1.675 0.307 29.756 5.338 2.924～9.744 <0.001
TNM分期 1.184 0.335 12.488 3.268 1.694～6.302 <0.001
肿瘤直径 0.841 0.276 9.259 2.319 1.349～3.985 0.002
Ki67 0.766 0.294 6.789 2.150 1.209～3.825 0.009
脉管癌栓 2.082 0.294 50.154 8.024 4.509～14.278 <0.001
年龄 0.301 0.263 1.308 1.351 0.807～2.260 0.253
激素受体 0.343 0.289 1.415 1.409 0.801～2.481 0.234
HER-2 0.490 0.280 3.066 1.632 0.943～2.825 0.080
组织学分级 0.253 0.284 0.792 1.287 0.738～2.245 0.374
表4 影响乳腺癌患者无瘤生存的多因素分析(n＝520)
临床病理因素 回归系数 标准误 Wald值 风险比 95%置信区间 P值
FAR 1.441 0.273 27.921 4.226 2.476～7.212 <0.001
淋巴结 1.481 0.501 8.749 4.397 1.648～11.731 0.003
脉管癌栓 1.751 0.329 28.268 5.758 3.020～10.978 <0.001
表5 影响乳腺癌患者总生存的单因素分析(n＝520)
临床病理因素 回归系数 标准误 Wald值 风险比 95%置信区间 P值
FAR 1.363 0.364 13.996 3.907 1.913～7.978 <0.001
淋巴结 1.589 0.411 14.942 4.897 2.188～10.957 <0.001
TNM分期 1.172 0.455 6.638 3.229 1.324～7.875 0.010
肿瘤直径 1.100 0.396 7.719 3.004 1.383～6.527 0.005
Ki67 0.838 0.411 4.165 2.311 1.034～5.187 0.041
脉管癌栓 1.396 0.364 14.690 4.039 1.978～8.249 <0.001
年龄 0.278 0.360 0.596 1.320 0.652～2.670 0.440
激素受体 -0.004 0.430 0.000 0.996 0.429～2.313 0.993
HER-2 0.705 0.369 3.655 2.024 0.982～4.170 0.056
组织学分级 -0.004 0.410 0.000 0.996 0.445～2.227 0.992
表6 影响乳腺癌患者总生存的多因素分析(n＝520)
临床病理因素 回归系数 标准误 Wald值 风险比 95%置信区间 P值
FAR 1.463 0.371 15.536 4.320 2.087～8.942 <0.001
淋巴结 1.567 0.628 6.220 4.790 1.399～16.407 0.013
肿瘤直径 1.213 0.613 3.918 3.363 1.012～11.179 0.048
脉管癌栓 0.848 0.400 4.497 2.335 1.066～5.111 0.034
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