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中华临床实验室管理电子杂志 ›› 2025, Vol. 13 ›› Issue (03) : 149 -158. doi: 10.3877/cma.j.issn.2095-5820.2025.03.004

实验研究

不同临床特征和内分泌治疗药物对乳腺癌患者凝血功能的影响
吕冉1, 林晓东2, 宋金龙1, 陈婉君1, 韩秀晶1,()   
  1. 1 510120 广东 广州,广州医科大学附属第一医院检验科
    2 510120 广东 广州,广州医科大学附属第一医院病理科
  • 收稿日期:2024-07-09 出版日期:2025-08-28
  • 通信作者: 韩秀晶
  • 基金资助:
    广州市科学技术局市校(院)联合资助项目(202201020426)

The impact of different clinical characteristics and endocrine therapies on coagulation in breast cancer patients

Ran Lyu1, Xiaodong Lin2, Jinlong Song1, Wanjun Chen1, Xiujing Han1,()   

  1. 1 Laboratory department of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Guangdong 510120, China
    2 Pathology department of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Guangdong 510120, China
  • Received:2024-07-09 Published:2025-08-28
  • Corresponding author: Xiujing Han
引用本文:

吕冉, 林晓东, 宋金龙, 陈婉君, 韩秀晶. 不同临床特征和内分泌治疗药物对乳腺癌患者凝血功能的影响[J/OL]. 中华临床实验室管理电子杂志, 2025, 13(03): 149-158.

Ran Lyu, Xiaodong Lin, Jinlong Song, Wanjun Chen, Xiujing Han. The impact of different clinical characteristics and endocrine therapies on coagulation in breast cancer patients[J/OL]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2025, 13(03): 149-158.

目的

分析不同临床特征和内分泌治疗药物对乳腺癌患者凝血功能的影响。

方法

回顾性分析2016至2020年广州医科大学附属第一医院收治的209例女性乳腺浸润性导管癌患者临床资料和病理特征与凝血的关系,并进一步分析不同内分泌治疗药物治疗前后患者的凝血相关指标变化。

结果

治疗前,209例乳腺浸润性导管癌患者中,年龄>55岁的纤维蛋白原(FIB)、凝血酶时间(TT)水平高于年龄≤55岁的患者,绝经患者的FIB、TT水平高于未绝经患者;淋巴结转移组与未转移组相比,凝血指标差异无统计学意义(P>0.05);TNM分期Ⅲ~Ⅳ期患者的血浆凝血酶原时间、国际标准化比值、TT和PLT高于Ⅰ~Ⅱ期患者,凝血酶原活动度低于Ⅰ~Ⅱ期患者(P<0.05);雌激素受体、孕激素受体、人表皮生长因子受体-2、Ki-67抗原不同表达强度之间相比,各项凝血指标、PLT值和红细胞分布宽度-变异系数(RDW-CV)差异无统计学意义(P>0.05)。内分泌药物治疗前后相比,芳香化酶抑制剂(AI)组患者治疗后RDW-CV低于治疗前(P<0.05);他莫昔芬(TAM)组患者治疗后活化部分凝血酶原时间(APTT)、RDW-CV和PLT值低于治疗前,TT高于治疗前(P<0.05);托瑞米芬(TOR)组患者治疗后APTT和RDW-CV低于治疗前(P<0.05);联合用药组患者治疗后TT高于治疗前,PLT值低于治疗前,差异均有统计学意义(均P<0.05)。

结论

乳腺浸润性导管癌患者年龄高、绝经、TNM分期高是高凝状态的危险因素。TAM和TOR具有促凝作用,联合用药有促凝趋势,AI对凝血无明显影响。监测凝血指标,对乳腺浸润性导管癌患者治疗药物的选择和优化治疗方案有积极意义。

Objective

To analyze the impact of different clinical characteristics and endocrine drugs on blood coagulation in breast cancer patients.

Methods

The clinical data and pathological features of 209 female patients with breast invasive ductal carcinoma treated at the First Affiliated Hospital of Guangzhou Medical University from 2016 to 2020 were retrospectively analyzed. Associations between clinicopathological features and coagulation parameters were evaluated, with longitudinal assessment of coagulation changes before and after endocrine therapy.

Results

Among the 209 patients with invasive ductal carcinoma of the breast prior to treatment, the levels of fibrinogen (FIB) and thrombin time (TT) were higher in patients older than 55 years compared to those 55 years or younger. Additionally, postmenopausal patients exhibited higher levels of FIB and TT than non-menopausal patients. However, there was no significant difference in coagulation indicators between the lymph node metastasis group and the non-metastatic group (P>0.05). In patients with tumor node metastasis classification (TNM) stage Ⅲ-Ⅳ breast cancer, levels of prothrombin time, international normalized ratio, TT, and PLT were higher than those in stage Ⅰ-Ⅱ patients. Conversely, prothrombin time test activity levels were lower (P<0.05). There was no significant difference in various coagulation indicators, PLT value, and red cell distribution width-coefficient of variation (RDW-CV) between different expression intensities of estrogen receptor, progestin recetor, human epidermal growth factorreceptor 2, and Ki-67 (P>0.05). After endocrine therapy, RDW-CV levels were lower in patients treated with aromatase inhibitor (AI) compared to pre-therapy levels (P<0.05). The levels of activated partial thromboplastin time (APTT), RDW-CV and PLT in patients treated with tamoxifen (TAM) were lower while TT was higher than those in pre-therapy (P<0.05). The levels of APTT and RDW-CV in patients treated with toremifene (TOR) were lower than those in pre-therapy (P<0.05). The TT of patients receiving combination therapy was higher, while the PLT level was lower than that in pre-therapy (P<0.05).

Conclusions

Advanced age, menopause and higher TNM stage are risk factors for hypercoagulability in patients with invasive ductal carcinoma of the breast. TAM and TOR exert procoagulant effects, and the combination therapy has a tendency to promote coagulation, while AI minimally affects coagulation. Monitoring the coagulation indicators is essential for selecting treatment options and optimizing care for patients with invasive ductal carcinoma of the breast.

表1 患者一般资料及其他临床病理特征
临床特征 入组患者(n=209)/例(%) 接受内分泌治疗(n=81)
Ⅰ~Ⅱ期/例(%) Ⅲ~Ⅳ期/例(%)
年龄/岁
≤55 125(59.8) 40(58.0) 6(50.0)
>55 84(40.2) 29(42.0) 6(50.0)
淋巴结转移
101(48.3) 44(63.8) 1(8.3)
108(51.7) 25(36.2) 11(91.7)
TNM分期
Ⅰ~Ⅱ期 140(67.0) 69(100.0) /
Ⅲ~Ⅳ期 69(33.0) / 12(100.0)
月经状态
已绝经 121(57.9) 43(62.3) 9(75.0)
未绝经 88(42.1) 26(37.7) 3(25.0)
ER状态
阴性 61(29.2) 4(5.8) 3(25.0)
阳性 148(70.8) 65(94.2) 9(75.0)
PR状态
阴性 93(44.5) 20(29.0) 3(25.0)
阳性 116(55.5) 49(71.0) 9(75.0)
Her-2表达
0 38(18.2) 15(21.7) 3(25.0)
1+ 47(22.5) 18(26.1) 0(0.0)
2+ 60(28.7) 26(37.7) 3(25.0)
3+ 64(30.6) 10(14.5) 6(50.0)
Ki-67抗原
11(5.3) 1(1.4) 1(8.3)
低表达 13(6.2) 6(8.7) 1(8.3)
高表达 102(48.8) 27(39.1) 7(58.3)
中等表达 83(39.7) 35(50.7) 3(25.0)
内分泌治疗
90(43.1) 0(0.0) 0(0.0)
119(56.9) 69(100.0) 12(100.0)
治疗药物
92(44.0) 0(0.0) 0(0.0)
AI 58(27.8) 34(49.3) 7(58.3)
TAM 10(4.8) 7(10.1) 1(8.3)
TOR 32(15.3) 19(27.5) 2(16.7)
联合用药 17(8.1) 9(13.0) 2(16.7)
静脉血栓
206(98.6) 68(98.6) 12(100.0)
3(1.4) 1(1.4) 0(0.0)
图1 不同临床特征对部分凝血相关参数的影响 注:与≤55岁组比较,aP<0.05;与未绝经组比较,aP<0.05;与Ⅰ~Ⅱ期组比较,aP<0.05。
表2 乳腺浸润性导管癌患者基本临床特征与凝血相关指标的比较分析(n=209)
指标 年龄/岁 月经状态
≤ 55(n=125) >55(n=84) Z/t P 已绝经(n=121) 未绝经(n=88) Z/t P
PT/s 13.10(12.80,13.60) 13.10(12.73,13.70) -0.224 0.823 13.10(12.75,13.60) 13.25(12.80,13.70) -1.187 0.235
INR 1.00(0.96,1.04) 0.99(0.96,1.04) -0.127 0.899 0.99(0.96,1.04) 1.01(0.96,1.05) -1.065 0.287
PTTA/% 100.82±11.11 101.21±12.37 0.153 0.879 102.00(94.00,108.50) 99.50(92.25,107.00) -1.158 0.247
APTT/s 36.90(35.10,39.55) 36.85(34.43,38.78) -1.087 0.277 36.90(34.50,38.75) 36.95(35.13,39.83) -1.356 0.175
FIB/g/L 3.28(2.84,3.79) 3.76(3.35,4.25) -4.903 <0.001 3.68(3.30,4.11) 3.18(2.81,3.77) -4.987 <0.001
TT/s 16.6(16.00,17.20) 17.00(16.33,17.50) -2.794 0.005 16.90(16.35,17.50) 16.50(16.00,17.15) -3.288 0.001
PLT/(×109/L) 262.83±59.69 245.83±67.05 1.920 0.056 251.00(210.00, 283.50) 257.92(225.25, 301.25) -1.460 0.144
RDW-CV/% 13.40(12.70,14.20) 13.40(13.00,14.08) -0.859 0.391 13.40(12.90,14.00) 13.40(12.80,14.65) -0.154 0.877
指标 淋巴结转移 TNM 分期
无(n=101) 有(n=108) Z/t P Ⅰ~Ⅱ(n=140) Ⅲ~Ⅳ(n=69) Z/t P
PT/s 13.00(12.80,13.60) 13.30(12.80,13.70) -1.459 0.145 13.10(12.70,13.60) 13.30(12.95,13.80) -2.950 0.003
INR 0.99(0.95,1.03) 1.01(0.96,1.05) -1.546 0.122 0.99(0.94,1.03) 1.01(0.98,1.06) -2.912 0.004
PTTA/% 103.00(94.50,109.50) 99.00(92.00,107.00) -1.547 0.122 102.80±11.36 97.28±11.27 3.314 0.001
APTT/s 36.70(34.60,38.55) 37.10(35.10,39.90) -1.361 0.174 36.70(34.80,38.80) 37.70(35.10,40.50) -1.570 0.116
FIB/g/L 3.48(2.97,4.03) 3.49(3.05,3.95) -0.199 0.842 3.42(2.99,3.90) 3.56(3.15,4.20) -1.807 0.071
TT/s 16.70(16.20,17.30) 16.75(16.03,17.68) -0.653 0.514 16.60(16.10,17.30) 17.10(16.2,17.80) -2.535 0.011
PLT/(×109/L) 248.00(210.00,282.00) 259.00(222.50,298.75) -1.391 0.164 247.50(210.00,282.50) 263.00(228.50,303.00) -2.037 0.042
RDW-CV/% 13.40(12.80,13.75) 13.40(12.90,14.58) -1.303 0.193 13.40(12.90,14.00) 13.40(12.80,14.55) -0.636 0.525
表3 年龄与月经状态、TNM分期的相关性分析/例(%)
表4 乳腺浸润性导管癌患者病理特征与凝血相关指标的比较分析(n=209)
指标 ER状态 PR状态
阴性(n=61) 阳性(n=148) Z/t P 阴性(n=93) 阳性(n=116) Z/t P
PT/s 13.10(12.75,13.65) 13.10(12.80,13.68) -0.459 0.647 13.18±0.76 13.24±0.67 -0.656 0.512
INR 0.99(0.96,1.05) 1.00(0.96,1.04) -0.184 0.854 0.99(0.95,1.04) 1.00(0.96,1.04) -0.622 0.534
PTTA/% 101.23±13.13 100.87±10.96 0.202 0.840 101.47±12.27 100.58±11.07 0.554 0.580
APTT/s 36.40(34.10,39.00) 36.95(35.10,39.38) -1.284 0.199 36.70(34.45,38.75) 37.05(35.13,39.68) -1.672 0.094
FIB/(g/L) 3.51(3.22,4.14) 3.49(2.92,3.94) -1.615 0.106 3.43(3.10,3.91) 3.50(2.97,4.04) -0.137 0.891
TT/s 16.70(16.10,17.55) 16.70(16.20,17.30) -0.031 0.975 16.8(16.20,17.40) 16.70(16.00,17.40) -0.311 0.756
PLT/(×109/L) 258.00(234.50,298.00) 250.50(207.50,291.50) -1.707 0.088 258.00(217.00,291.00) 249.50(212.00,292.75) -0.733 0.464
RDW-CV /% 13.40(12.90,15.10) 13.40(12.80,13.98) -1.279 0.201 13.40(12.90,14.20) 13.40(12.80,14.08) -1.272 0.203
指标 Her-2表达
0(n=38) 1+(n=47) 2+(n=60) 3+(n=64) H P
PT/s 13.20(12.78,13.68) 13.10(12.80,13.70) 13.25(12.83,13.70) 13.10(12.60,13.60) 1.106 0.776
INR 0.99(0.96,1.06) 0.99(0.96,1.04) 1.00(0.96,1.04) 0.99(0.94,1.05) 0.562 0.905
PTTA/% 100.71±13.92 101.68±10.35 100.17±10.78 101.38±11.93 0.677 0.879
APTT/s 36.45(34.15,39.48) 37.10(35.10,39.90) 36.90(35.15,38.60) 36.45(34.43,39.08) 1.599 0.660
FIB/(g/L) 3.68(3.01,4.14) 3.79(3.24,4.05) 3.39(2.87,3.72) 3.34(3.04,3.93) 7.565 0.056
TT/s 16.60(16.00,17.20) 16.70(16.30,17.40) 16.70(16.20,17.30) 16.80(16.00,17.68) 1.009 0.799
PLT/(×109/L) 242.00(204.75,293.25) 255.84(224.00,285.00) 248.00(201.00,298.00) 260.50(225.25,292.75) 1.847 0.605
RDW-CV /% 13.05(12.70,14.28) 13.40(13.00,14.20) 13.40(12.80,14.00) 13.40(12.93,14.58) 1.985 0.576
指标 Ki-67
无(n=11) 低表达(n=13) 高表达(n=102) 中介(n=83) H/F P
PT/s 13.25±0.62 13.39±0.56 13.17±0.77 13.23±0.67 0.396 0.756
INR 1.01±0.06 1.03±0.06 1.00±0.06 1.00±0.07 0.678 0.566
PTTA/% 99.73±9.59 96.23±9.05 101.80±12.56 100.87±10.92 0.942 0.421
APTT/s 35.10±2.24 38.26±2.02 37.49±4.76 37.49±4.76 1.416 0.239
FIB/(g/L) 3.08(2.68,3.58) 3.43(2.99,4.03) 3.48(3.15,3.91) 3.56(2.98,4.04) 2.132 0.546
TT/s 16.70(16.00,16.80) 16.60(16.25,17.05) 16.80(16.18,17.60) 16.80(16.10,17.40) 2.240 0.524
PLT/(×109/L) 246.52±17.53 252.31±21.36 261.58±5.81 250.57±7.36 0.549 0.650
RDW-CV /% 13.4(13.30,16.50) 13.20(12.45,14.35) 13.40(12.80,14.53) 13.40(12.90,13.80) 2.693 0.441
图2 不同内分泌治疗药物治疗前后凝血相关参数的变化 注:与治疗前比较,aP<0.05。
表5 Ⅰ~Ⅱ期患者内分泌治疗前后凝血相关指标水平比较(n=69)
项目 PT/% INR
AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9) AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9)
治疗前 13.10(12.48,13.70) 13.00(12.60,13.30) 13.50(12.80,13.80) 13.50(12.50,13.85) 1.00±0.08 0.97(0.94,1.01) 1.01±0.06 1.00(0.96,1.07)
治疗后 13.05(12.58,13.50) 12.80(12.50,13.10) 13.00(12.70,13.40) 13.10(12.45,13.35) 0.99±0.07 0.97(0.93,0.97) 0.99±0.05 1.01(0.94,1.03)
Z -0.300 -0.593 -1.653 -0.949 0.665 -1.051 1.288 -1.011
P 0.764 0.553 0.098 0.343 0.511 0.293 0.214 0.312
项目 PTTA/% APTT/s
AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9) AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9)
治疗前 102.32±13.90 106.14±7.65 99.11±9.49 99.00(89.00,108.50) 36.85(34.23,38.78) 36.40(34.00,41.10) 35.20(33.50,36.60) 38.98±3.04
治疗后 103.56±13.53 108.86±6.20 102.63±10.13 99.00(96.00,113.00) 37.30(34.25,38.73) 34.90(30.90,36.80) 33.40(31.80,35.60) 36.17±4.71
Z/t -0.549 -0.764 -1.279 -0.889 -0.479 -2.366 -1.992 1.631
P 0.587 0.474 0.217 0.374 0.632 0.018 0.046 0.141
项目 FIB/g/L TT/s
AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9) AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9)
治疗前 3.76(2.84,4.42) 3.30±0.69 3.49(3.10,4.11) 3.09±0.49 16.70(16.08,17.63) 16.90(15.50,17.60) 16.40(15.70,17.00) 16.00(15.75,16.70)
治疗后 3.44(2.95,4.03) 2.84±0.60 3.32(2.83,3.60) 3.07±0.79 17.15(16.48,17.75) 17.50(16.50,18.30) 16.70(15.90,17.90) 17.30(16.60,17.70)
Z/t -0.256 1.294 -1.389 0.077 -1.535 -2.371 -1.331 -2.073
P 0.798 0.243 0.165 0.941 0.125 0.018 0.183 0.038
项目 RDW-CV/% PLT(×109/L)
AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9) AI组(n=34) TAM组(n=7) TOR组(n=19) 联合用药组(n=9)
治疗前 14.10(13.20,14.73) 15.29±1.76 15.10(13.60,15.90) 15.90±3.47 236.50(206.00,290.75) 278.00±65.52 226.79±78.29 239.78±72.58
治疗后 13.35(12.78,14.10) 13.31±0.99 13.40(13.10,14.80) 13.94±1.07 231.00(211.75,277.00) 219.86±33.70 221.37±70.40 201.44±56.42
Z/t -2.438 3.936 -2.509 1.914 -0.339 2.833 0.340 2.561
P 0.015 0.008 0.012 0.092 0.734 0.030 0.738 0.034
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