Effect of indomethacin on immune function and coagulation of patients with metastatic breast cancer

Abstract

Objective To observe the effect of indomethacin on immune function and coagulation of patients with metastatic breast cancer. Methods 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. Results 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. Conclusions 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. Key words: Breast neoplasms; Neoplasm metastasis; Indomethacin; Immunity, cellular; Hemagglutination