观察吲哚美辛对转移性乳腺癌患者免疫功能及凝血状态的影响。

选取2015年7月至2017年12月期间复旦大学附属中山医院闵行分院乳腺外科收治的转移性乳腺癌女性患者27例进行前瞻性研究，给予口服吲哚美辛50 mg/次，每日3次，连用2周。另选在本院体检的健康女性30例作为对照组。流式细胞仪检测转移性乳腺癌患者用药前、后及对照组外周血T淋巴细胞亚群；血栓弹力图描记对照组及患者用药前、后凝血状态；记录转移性乳腺癌患者用药后的不良反应。以CD4^＋细胞比率、CD8^＋细胞比率、CD4^＋细胞数/CD8^＋细胞数及自然杀伤(NK)细胞活性作为免疫功能评价指标；以血栓弹力图的反应时间(R值)、α角(ANG)、最大振幅(MA)等参数为凝血状态指标。乳腺癌组患者用药前、后指标的比较采用配对t检验；乳腺癌组与健康对照组指标的比较采用独立样本t检验。

转移性乳腺癌患者外周血中CD4^＋细胞比率、CD4^＋细胞数/CD8^＋细胞数及NK细胞活性低于健康对照组[(28.76±4.03)%比(46.28±4.92)%，t＝－14.596，P<0.050; 0.78±0.22比1.65±0.34，t＝－11.303，P<0.050; (16.28±7.41)%比(34.73±16.39)%，t＝－5.370，P<0.050]，CD8^＋细胞比率则高于对照组[(36.35±3.76)%比(27.41±2.63)%，t＝10.483，P<0.050]；R值降低，ANG、MA升高[(3.52±0.84) min比(5.26±2.05)min，t＝－4.128，P<0.050；(75.74±8.41)°比(68.84±7.50)°，t＝3.270，P<0.050；(72.63±11.69) mm比(62.89±6.61) mm，t＝3.926，P<0.050]。口服吲哚美辛2周后转移性乳腺癌患者外周血中CD4^＋细胞比率、CD4^＋细胞数/CD8^＋细胞数及NK细胞活性分别为(37.55±3.64)%、1.20±0.18、(25.62±9.8)%，较用药前明显提升(t＝36.926、23.995、12.818，P<0.05], CD8^＋细胞比率为(31.42±2.58)%，较用药前明显下降(t＝－20.087，P<0.050)；R值、ANG、MA分别为(4.33±1.57) min、(67.12±9.36)°、(64.52±6.32) mm，R值较用药前升高，ANG、MA则降低(t＝5.210、－14.351、－6.677，P<0.050)。转移性乳腺癌患者用药期间3例出现头晕，7例胃部不适伴恶心呕吐，腹泻2例，未观察到严重不良反应。

转移性乳腺癌患者免疫功能严重受损，并处于病理性高凝状态。吲哚美辛应用可增强患者免疫功能，改善其凝血状态。

To observe the effect of indomethacin on immune function and coagulation of patients with metastatic breast cancer.

Totally 27 patients with metastatic breast cancer in the Department of Breast Surgery, Minhang Branch, Zhongshan Hospital, Fudan University from July 2015 to December 2017 were enrolled in this prospective study. They were treated with indomethacin at the dosage of 50 mg each time, three times per day, for continuous 14 days. Another 30 healthy individuals who received physical examination in our hospital served as control. Flow cytometry was used to detect the T-lymphocyte subgroups and thromboclastography was used to measure the coagulation of breast cancer patients before and after administration of indomethacin. The healthy individuals were also detected. The adverse reactions of patients with metastatic breast cancer after indomethacin administration were recorded. The proportion of CD4⁺ cells, CD8⁺ cells, the ratio of CD4⁺ cells/CD8⁺ cells and natural killer (NK) cell activity were evaluated as indexes of immune function; thromboclastographic parameters, including reaction time (R), α angle (ANG), maximum amplitude (MA), were evaluated as indexes of coagulation status. Paired t-test was used to compare the indicators of immune function and coagulation in the patients with metastatic breast cancer before and after indomethacin administration. The independent sample t-test was used to compare the above-mentioned indicators between breast cancer patients and healthy individuals.

The proportion of CD4⁺ cells, the ratio of CD4⁺ cells/CD8⁺ cells and NK cell activity in peripheral blood of breast cancer patients were significantly lower than those in healthy controls [(28.76±4.03)%vs (46.28±4.92)%, t=-14.596, P<0.050; 0.78±0.22 vs 1.65±0.34, t=-11.303, P<0.050; (16.28±7.41)%vs (34.73±16.39)%, t=-5.370, P<0.050], while the proportion of CD8⁺ cells was significantly higher than that in healthy controls [(36.35±3.76)%vs (27.41±2.63)%, t=10.483, P<0.050]. The thromboclastography showed that R, ANG and MA of breast cancer patients were significantly different from those of healthy controls [(3.52±0.84)min vs (5.26±2.05)min, t=-4.128, P<0.050; (75.74±8.41)°vs (68.84±7.50)°, t=3.270, P<0.050; (72.63±11.69) mm vs (62.89±6.61) mm, t=3.926, P<0.050]. After the treatment of indomethacin for 2 weeks, the proportion of CD4⁺ cells, the ratio of CD4⁺ cells/CD8⁺ cells and NK cell activity in breast cancer group [(37.55±3.64)%, 1.20±0.18, (25.62±9.8)%]were significantly higher than those in control group(t=36.926, 23.995, 12.818, P<0.05); and the proportion of CD8⁺ cells [(31.42±2.58)%] was significantly lower (t=-20.087, P<0.050); the values of R, ANG and MA of breast cancer patients were (4.33±1.57) min, (67.12±9.36)° and (64.52±6.32) mm, respectively, indicating that R was significantly increased and ANG and MA were significantly decreased compared with the control group (t=5.210, -14.351, -6.677, P<0.050). During the period of indomethacin administration, 3 patients had dizziness, 7 patients had stomach distress and vomiting and 2 patients had diarrhea. No severe adverse reactions were observed.

The patients with metastatic breast cancer have seriously impaired immune function and pathological hypercoagulable state. Indomethacin can improve the immune function and coagulation status of patients with metastatic breast cancer.