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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (06) : 353 -357. doi: 10.3877/cma.j.issn.1674-0807.2016.06.006

论著

血清肝细胞生长因子对Ⅱ/Ⅲ期乳腺癌新辅助化疗疗效及预后的影响
赵华洲1, 王婷2, 张心慧1, 刘瑞军1, 曹志宇1, 杨波1, 何建苗1,†()   
  1. 1.100091 北京,解放军第309 医院普通外科
    2.100020 首都医科大学附属北京朝阳医院医务处
  • 收稿日期:2016-03-08 出版日期:2016-12-01
  • 通信作者: 何建苗

Impact of serum hepatocyte growth factor on response to neoadjuvant chemotherapy and prognosis in patients with stage Ⅱ/Ⅲbreast cancer

Huazhou Zhao1, Ting Wang2, Xinhui Zhang1, Ruijun Liu1, Zhiyu Cao1, Bo Yang1, Jianmiao He1,†()   

  1. 1.Department of General Surgery, No. 309 Hospital of PLA, Beijing 100091, China
    2.Department of Medical Affairs, Beijing Chaoyang Hospital, Capital Medical University,Beijing 100020, China
  • Received:2016-03-08 Published:2016-12-01
  • Corresponding author: Jianmiao He
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赵华洲, 王婷, 张心慧, 刘瑞军, 曹志宇, 杨波, 何建苗. 血清肝细胞生长因子对Ⅱ/Ⅲ期乳腺癌新辅助化疗疗效及预后的影响[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(06): 353-357.

Huazhou Zhao, Ting Wang, Xinhui Zhang, Ruijun Liu, Zhiyu Cao, Bo Yang, Jianmiao He. Impact of serum hepatocyte growth factor on response to neoadjuvant chemotherapy and prognosis in patients with stage Ⅱ/Ⅲbreast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(06): 353-357.

目的

探讨血清肝细胞生长因子(HGF)与乳腺癌临床病理特征及新辅助化疗(NAC)疗效间的关系。

方法

回顾性收集2010年1月至2015年1月168 例于解放军第309 医院因Ⅱ/Ⅲ期乳腺癌行新辅助化疗的患者资料,采用ELISA 法检测患者血液样本中HGF 浓度,统计分析血清HGF 水平中位值,将血清HGF 高于中位值患者设为高水平(H)组(n=84),血清HGF 低于中位值患者设为低水平(L)组(n=84)。 依据实体瘤治疗疗效评价(RECIST)标准评估患者接受NAC 的疗效。 患者术后随访时间2 ～68 个月,制作患者生存曲线。 采用χ2 检验比较2 组患者临床分期、肿瘤直径、淋巴结转移、ER、PR 及HER-2 状态间的差异,采用t 检验比较2 组患者组织多肽特异性抗原(TPSA)、糖链抗原(CA)15-3、Ki67 间的差异,采用Kaplan-Meier 法分析血清HGF 水平与NAC 疗效、5年累积生存率及5年DFS 的差异的关系,采用Cox 比例风险回归模型分析影响5年累积生存率的风险因素。

结果

患者血清HGF 中位值为825 pg/ml。 H 组淋巴结转移率为48.8%(41/84)、血清TPSA 为(60.6±26.8)U/L,高于L 组的30.9%(26/84)(χ2=5.586,P=0.018)和(49.8±20.9)U/L(t=-2.930,P=0.004)。 Kaplan-Meier 法提示H 组化疗有效率为69.0%(58/84)、5年DFS 为65.5%、5年累积生存率分别为69.0%,低于L 组的84.5%(71/84)(χ2 =5.643,P=0.018)、81.9% (χ2 =4.957, P=0.046)和89.9% (χ2 =4.849, P=0.044)。 Cox 比例风险回归模型分析提示血清HGF 水平、临床分期及NAC 疗效是影响5年累积生存率的风险因素(HR=7.0,95%CI=1.28 ～47.62, P=0.037; HR=8.5, 95%CI=3.55 ～29.79, P=0.006;HR=4.8,95%CI=1.84 ～7.99, P=0.024)。

结论

血清HGF 水平与乳腺癌淋巴结转移、NAC 疗效及预后密切相关,可作为预测NAC 疗效和预后的指标。

关键词: 肝细胞生长因子, 乳腺肿瘤, 抗肿瘤联合化疗方案新辅助化疗, 淋巴转移, 无病生存

Objective

To explore the relationship of serum hepatocyte growth factor (HGF) with the efficacy of neoadjuvant chemotherapy (NAC) and clinicopathological characteristics in patients with stage Ⅱ/Ⅲbreast cancer.

Methods

Totally 168 patients with stage Ⅱ/Ⅲbreast cancer who underwent neoadjuvant therapy between January 2010 and January 2015 in No. 309 Hospital of PLA were enrolled for a retrospective study. They were divided into 2 groups, including low HGF level (L) group (n=84) and high HGF level(H) group (n = 84) according to the median value of serum HGF, which was detected by ELISA and calculated by statistical analysis. The efficacy of NAC was assessed according to the RECIST criteria. The patients were followed up for 2-68 months and the survival curves were drawn. The differences in clinical stage, tumor size, lympho node metastasis, ER, PR and HER-2 expression between two groups were analyzed by χ2 test. The differences in tissue polypeptide specific antigen (TPSA), carbohydrate antigen (CA) 15-3,Ki67 were analyzed by t test. Kaplan-Meier method was used to analyze the relationship of serum HGF level with efficacy of NAC, 5-year DFS and 5-year cumulative survival. Risk factors associated with 5-year cumulative survival were processed in Cox's proportional hazards regression model.

Results

Serum HGF level had a median value of 825 pg/ml. The rate of lympho node metastasis in H group was 48.8% (41/84),significantly higher than 30.9% (26/84) in L group (χ2=5.586,P=0.018). Serum TPSA level in H group was (60.6±26.8) U/L,significantly higher than (49.8±20.9) U/L in L group (t=-2.93,P=0.004). The efficacy of NAC,5-year DFS and 5-year cumulative survival in H group was 69.0%(58/84), 65.5% and 69.0% respectively, significantly lower than 84.5%(71/84),81.9% and 89.9% in L group (χ2=5.643,P=0.018;χ2 =4.957, P=0.046;χ2 =4.849, P=0.044). Serum HGF level, clinical stage and NAC response were risk factors of 5-year cumulative survival (HR=7.0, 95%CI=1.28-47.62, P=0.037; HR=8.5,95%CI=3.55-29.79, P=0.006; HR=4.8, 95%CI=1.84-7.99, P=0.024).

Conclusion

Serum HGF level is closely associated with lymph node metastasis, response to NAC and prognosis in patients with breast cancer, which can be used as a predictive index for NAC efficacy and patients' prognosis.

Key words: Hepatocyte growth factor, Breast neoplasms, Antineoplastic combined chemotherapy protocols, Lymphatic metastasis, Disease-free survival
表1 影响乳腺癌患者5年累积生存率的危险因素赋值表
变量 变量分类及赋值
血清HGF水平 ≤825pg/ml=0,＞825pg/ml=1
临床分期 Ⅱ期=0,Ⅲ期=1
NAC疗效 有效=0,无效=1
表2 不同血清HGF 水平分组乳腺癌患者检测指标比较(±s )
分组 例数 检测指标
年龄(岁) CA15-3(U/ml) TPSA(U/L) Ki67(%)
L组 84 44.9±6.6 27.3±15.4 49.8±20.9 48.5±25.9
H组 84 44.6±6.0 26.8±13.7 60.6±26.8 44.0±23.3
t值 0.318 0.210 -2.930 1.180
P值 0.751 0.834 0.004 0.240
表3 血清HGF 水平与乳腺癌临床特征的关系(例)
临床特征 L组(n=84) H组(n=84) 检验值 P值
临床分期
Ⅱ 25 27 χ2=0.111 0.739
Ⅲ 59 57
肿瘤直径
≤5cm 44 46 χ2=0.096 0.757
＞5cm 40 38
淋巴结转移
无 58 43 χ2=5.586 0.018
有 26 41
ER
阳性 53 49 χ2=0.399 0.527
阴性 31 35
PR
阳性 48 44 χ2=0.384 0.535
阴性 36 40
HER-2
阳性 22 18 χ2=0.525 0.469
阴性 62 66
三阴性乳腺癌
是 16 14 χ2=0.162 0.687
否 68 70
图1 L 组和H 组乳腺癌患者5年DFS 的比较 注:L 组为肝细胞生长因子水平低表达组;H 组为肝细胞生长因子水平高表达组;χ2 =4.957,P=0.046;DFS 表示无瘤生存率
图2 L 组和H 组乳腺癌患者5年累积生存率的比较 注:L 组为肝细胞生长因子水平低表达组;H 组为肝细胞生长因子水平高表达组;χ2=4.849,P=0.044
表4 影响乳腺癌患者5年累积生存率的Cox 风险比例回归模型
变量 回归系数 标准误 Wald值 P值 HR值 95%置信区间
血清HGF水平 0.084 0.039 4.603 0.037 7.0 1.28～47.62
临床分期 0.459 0.159 5.459 0.006 8.5 3.55～29.79
NAC疗效 0.097 0.075 4.841 0.024 4.8 1.84～7.99
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