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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (06) : 349 -353. doi: 10.3877/cma.j.issn.1674-0807.2017.06.006

论著

三阴性乳腺癌患者凝血相关指标的检测及其临床意义
张萍1, 陆肖玮1, 宋卫1, 丁云1, 毛锦锋1, 马涛1,†()   
  1. 1.214002 江苏省无锡市妇幼保健院乳腺科
  • 收稿日期:2017-03-02 出版日期:2017-12-01
  • 通信作者: 马涛

Determination of coagulation-related parameters in triple negative breast cancer and clinical significance

Ping Zhang1, Xiaowei Lu1, Wei Song1, Yun Ding1, Jinfeng Mao1, Tao Ma1,†()   

  1. 1.Department of Breast Diseases, Wuxi Women and Children's Hospital, Wuxi 214002, China
  • Received:2017-03-02 Published:2017-12-01
  • Corresponding author: Tao Ma
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张萍, 陆肖玮, 宋卫, 丁云, 毛锦锋, 马涛. 三阴性乳腺癌患者凝血相关指标的检测及其临床意义[J/OL]. 中华乳腺病杂志(电子版), 2017, 11(06): 349-353.

Ping Zhang, Xiaowei Lu, Wei Song, Yun Ding, Jinfeng Mao, Tao Ma. Determination of coagulation-related parameters in triple negative breast cancer and clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2017, 11(06): 349-353.

目的

探讨三阴性乳腺癌(TNBC)患者凝血相关指标及其临床意义。

方法

依据患者的纳入和排除标准,收集2015 年1 月至2016 年8 月无锡市妇幼保健院收治的174 例Ⅰ～Ⅲa 期乳腺癌患者的病历资料进行回顾性研究。 依据乳腺癌分子分型标准将患者分为luminal A 型组32 例、luminal B 型组55 例、HER-2 过表达型组37 例和TNBC 组50 例。 另外纳入乳腺良性肿瘤患者36 例为对照组。 分析治疗前各入组患者的血浆凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间国际标准化比值(PT-INR)、纤维蛋白原(Fib) 定量、血小板计数(BPC)等指标。 凝血指标数据以¯x±s 表示,多组间均数比较采用单因素方差分析,2 组均数比较采用t 检验,两两比较采用LSD 法。

结果

4 组间凝血相关指标APTT、PT、PT-INR、Fib 及TT 差异有统计学意义(F=3.083、4.680、8.272、5.426、3.919,P 均＜0.050),而BPC 差异无统计学意义(F=1.326,P=0.265)。 TNBC 组与对照组比较,APTT、PT、PT-INR 显著降低[(25.92±2.80) s 比(27.76±3.84) s,P＜0.050;(11.77±0.68) s 比(12.27±0.87) s,P＜0.050;(0.99±0.59) s 比(1.05±0.75) s,P＜0.050],而Fib 和TT 显著升高[(2.59±0.45) s比(2.12±0.42) s,P＜0.050;(20.07±1.31) s 比(19.20±1.39) s,P＜0.050]。 TNBC 组患者与luminal B型组比较,PT、PT-INR 降低[(11.77±0.68) s 比(12.21±0.69) s,P＜0.050;(0.99±0.59) s 比(1.04±0.06) s,P＜0.050],Fib 升高、TT 延长[(2.59±0.45) s 比(2.37±0.58) s,P＜0.050;(20.07±1.31) s 比(19.22±1.26) s,P＜0.050];TNBC 组与HER-2 过表达组比较,TT 延长[(20.07±1.31) s 对(19.50±1.31) s,P＜0.050]。 TNBC 患者中,有淋巴结转移者较无淋巴结转移者APTT 缩短[(24.12±0.75) s 比(26.43±2.70) s,t=-2.550,P=0.014];绝经后患者较绝经前患者PT 缩短[(11.65±0.70) s 比(12.08±0.55) s,t=-2.094,P=0.042],PT-INR 降低[(0.98±0.61) s 比(1.02±0.44) s,t=-2.272,P=0.028]。肿瘤直径≤2 cm 者与＞2 ～5 cm 者比较,各凝血指标APTT、PT、PT-INR、Fib 及TT 差异无统计学意义(t=-0.946、0.225、-1.321、-1.098、-1.376、-1.820,P 均＞0.050)。

结论

乳腺癌患者机体呈高凝状态,三阴性乳腺癌患者高凝状态更加显著, 绝经后及有淋巴结转移的三阴性乳腺癌患者有血栓形成风险。

关键词: 乳腺肿瘤, 血液凝固, 分子分型, 静脉血栓形成

Objective

To investigate the coagulation-related parameters in triple negative breast cancer (TNBC) patients and the clinical significance.

Methods

According to the inclusion and exclusion criteria,174 patients with stage Ⅰto Ⅲa breast cancer in Wuxi Women and Children's Hospital from January 2015 to August 2016 were involved in this retrospective study. Based on molecular subtypes, there were 32 patients with luminal A subtype,55 luminal B,37 HER-2 overexpression and 50 TNBC. Another 36 patients with benign breast tumor served as control group. Before treatment, their whole blood and serum samples were collected for measuring the coagulation-related parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time(TT), prothrombin time-international normalized ratio (PTINR), fibrinogen (Fib), and blood platelet count (BPC). All parameters were expressed as ±s and compared among multiple groups using single factor analysis of variance.The mean values between two groups were compared using t test and pairwise comparison was performed using LSD method.

Results

There were significant differences in APTT, PT, PT-INR, Fib and TT among groups (F=3.083,4.680,8.272,5.426,3.919, P＜0.050), but there was no significant difference in BPC (F=1.326, P=0.265). The patients in TNBC group had significantly lower levels of APTT, PT and PT-INR than those in control group [(25.92±2.80) s vs (27.76±3.84) s, P ＜0.050; (11.77±0.68) s vs (12.27±0.87) s, P＜0.050; (0.99±0.59)s vs (1.05±0.75) s, P ＜0.050], while Fib and TT were significantly higher [(2.59±0.45) s vs (2.12±0.42) s, P＜0.050; (20.07±1.31) s vs (19.20±1.39) s, P＜0.050]. The patients in TNBC group had significantly lower PT and PT-INR compared with luminal B group [(11.77±0.68) s vs (12.21±0.69) s, P ＜0.050; (0.99±0.59) s vs (1.04±0.06) s, P＜0.050], and significantly higher Fib and TT [(2.59±0.45) s vs (2.37±0.58) s, P＜0.050;(20.07±1.31) s vs (19.22±1.26) s, P ＜0.050]. The patients in TNBC group had significantly increased TT compared with HER-2 overexpression group [(20.07±1.31) s vs (19.50±1.31) s, P ＜0.050]. In TNBC group, the patients with lymph node metastasis had lower APTT than those without lymph node metastasis[(24.12±0.75) s vs (26.43±2.70) s, t = -2.550, P = 0.014]; the postmenopausal patients had lower PT and PT-INR compared with premenopausal patients [(11.65±0.70) s vs(12.08±0.55) s, t=-2.094,P=0.042; (0.98±0.61) s vs (1.02±0.44) s, t=-2.272,P=0.028]. The coagulation-related parameters (APTT,PT,PT-INR,Fib and TT) showed no significant difference between the patients with tumor diameter ≤2 cm and the patients with tumor diameter ＞2 cm but ≤5 cm (t=-0.946,0.225, -1.321, -1.098, -1.376, -1.820, all P＞0.050).

Conclusions

The breast cancer patients have hypercoagulable state, especially TNBC. The postmenopausal TNBC patients or the patients with lymph node metastasis may be in risk of thrombosis.

Key words: Breast neoplasms, Blood coagulation, Molecular typing, Venous thrombosis
表1 各乳腺癌组及良性肿瘤组患者的基线资料比较
组别 例数 年龄(岁,x¯±s) BMI(kg/m2,x¯±s) 临床分期(例) 病理类型(例) 组织学分级(例)
Ⅰ期 Ⅱ期 Ⅲ期 浸润性癌 DCIS 1级 2级 3级
TNBC组 50 53.5±10.9 25.2±3.1 28 21 1 48 2 33 16 1
luminal A组 32 53.0±9.0 24.7±3.6 24 7 1 29 3 24 7 1
luminal B组 55 50.6±9.5 24.6±3.4 30 23 2 46 9 36 17 2
HER-2过表达组 37 55.3±9.1 25.0±3.0 26 11 0 33 4 26 11 0
良性肿瘤组 36 49.3±10.5 23.9±2.6 - - - - - - - -
检验值 F=2.336 F=1.085 Z=5.362 χ2=4.360 Z=1.056
P值 0.057 0.365 0.147 0.225 0.788
表2 不同分型乳腺癌患者凝血指标的比较(±s)
组别 例数 APTT(s) Fib(g/l) PT(s) PT-INR TT(s) BPC(×109/L)
TNBC组 50 25.92±2.80a 2.59±0.45a,b 11.77±0.68a,b 0.99±0.59a,b 20.07±1.31a,b,c 232.60±57.89
luminal A组 32 25.40±3.06a 2.40±0.45a 11.84±0.54a,b 1.01±0.05a,b 19.64±0.83 222.19±54.04
luminal B组 55 25.56±3.06a 2.37±0.58a 12.21±0.69 1.04±0.06 19.22±1.26 217.87±53.02
HER-2过表达组 37 26.17±3.64a 2.62±0.72a,b 11.87±0.66a,b 1.01±0.06a,b 19.50±1.31 206.43±51.40
良性肿瘤组 36 27.76±3.84 2.12±0.42 12.27±0.87 1.05±0.75 19.20±1.39 225.94±59.04
F值 3.083 5.426 4.680 8.272 3.919 1.326
P值 0.017 ＜0.001 0.001 ＜0.001 0.004 0.265
表3 三阴性乳腺癌患者不同亚组凝血相关指标的比较(±s)
组别 例数 APTT(s) Fib(g/l) PT(s) PT-INR TT(s) BPC(×109/L)
淋巴结状态
转移 11 24.12±0.75 2.71±0.38 11.86±0.84 0.99±0.07 20.43±2.13 239.64±65.35
未转移 39 26.43±2.70 2.55±0.47 11.75±0.64 0.99±0.05 19.97±0.99 230.62±56.39
t值 -2.550 1.051 0.502 0.279 1.020 -0.453
P值 0.014 0.299 0.618 0.782 0.313 0.653
肿瘤直径
≤2cm 29 26.24±2.97 2.58±0.44 11.88±0.70 1.00±0.06 19.86±1.08 220.21±53.42
＞2～5cm 21 25.48±2.55 2.61±0.48 11.62±0.64 0.98±0.57 20.37±1.55 249.71±60.70
t值 -0.946 0.225 -1.321 -1.098 -1.376 -1.820
P值 0.349 0.823 0.193 0.278 0.178 0.075
患病年龄
绝经前 15 25.46±3.05 2.58±0.42 12.08±0.55 1.02±0.44 19.64±1.10 246.00±47.75
绝经后 35 25.95±32.69 2.56±0.46 11.65±0.70 0.98±0.61 20.31±1.35 223.89±56.29
t值 0.572 -0.145 -2.094 -2.272 1.680 -1.329
P值 0.570 0.885 0.042 0.028 0.099 0.190
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