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中山市人民医院乳腺外科,广东,中山,528403
网络出版:2014-02-20,
纸质出版:2013
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桂安萍,凌飞海,郑书楷. 紫杉醇对早期乳腺癌患者外周血淋巴细胞的影响[J]. 中国癌症杂志, 2013, 23(9): 737-743.
桂安萍, 凌飞海, 郑书楷. The effect of paclitaxel on the peripheral blood lymphocytes in early stage breast cancer[J]. China Oncology, 2013, 23(9): 737-743.
桂安萍,凌飞海,郑书楷. 紫杉醇对早期乳腺癌患者外周血淋巴细胞的影响[J]. 中国癌症杂志, 2013, 23(9): 737-743. DOI: 10.3969/j.issn.1007-3969.2013.09.008.
桂安萍, 凌飞海, 郑书楷. The effect of paclitaxel on the peripheral blood lymphocytes in early stage breast cancer[J]. China Oncology, 2013, 23(9): 737-743. DOI: 10.3969/j.issn.1007-3969.2013.09.008.
背景与目的:免疫功能是影响乳腺癌预后的重要因素之一。外周血及肿瘤内浸润的杀伤性T细胞计数能够预示乳腺癌的总生存率。另外,辅助化疗亦是提高术后乳腺癌患者无复发生存率及总生存率的重要环节。选择既对肿瘤细胞具有足够的杀伤作用,又能最大限度保留患者免疫功能的化疗药物对提高乳腺癌患者生存率具有重大意义。本研究旨在比较两种化疗方案,即蒽环类药物为主的CEF(环磷酰胺、表柔比星、5-氟尿嘧啶)方案以及蒽环类药物联合紫杉醇的EC序贯P(紫杉醇)方案对早期乳腺癌患者外周血淋巴细胞的影响。方法:回顾性分析自2012年11月—2013年5月在中山市人民医院乳腺外科行CEF方案(CEF组,n=20)或者EC序贯P方案(EC-P组,n=22)的早期乳腺癌术后患者的临床病理特征以及化疗前后患者外周血淋巴细胞的变化。关注的外周血淋巴细胞指标包括:总淋巴细胞计数以及T淋巴细胞、杀伤性T细胞、辅助性T细胞、活化T细胞和自然杀伤(NK)细胞的比例。结果:EC-P组患者较高危,临床分期、肿瘤大小、腋窝淋巴结状况、雌孕激素受体表达水平、组织分型等差异均有统计学意义(P<0.05)。化疗前,两组患者的各项外周血淋巴细胞指标差异无统计学意义。化疗过程中,CEF组患者化疗4个及5个疗程后,外周血淋巴细胞总数分别为(1 077±359)个/μL和(1 181±271)个/μL,明显较化疗前[(1 607±322)个/μL]减少,差异有统计学意义(P0.05)。EC-P组患者化疗4个及5个疗程后,外周血淋巴细胞总数分别为(1 500±312)个/μL和(1 623±468)个/μ L,与化疗前[(1 746±576)个/μ L]比较,差异无统计学意义(P0.05)。两组活化T细胞比例均随化疗疗程升高,CEF组化疗前(11.8±7.1)%,第5个疗程后(23±9.3)%,差异有统计学意义(P0.05);EC-P组化疗前(11.8±5.8)%,第5个疗程后(17.6±8.2)%,差异有统计学意义(P0.05)。在EC-P组中,序贯使用1次紫杉醇后,辅助性T细胞比例为(37.8±5.7)%,较化疗前[(41.3±4.3)%]及使用紫杉醇前[(41.9±5.6)%]均显著下降(P0.05);NK细胞比例为(21.5±5.2)%,较化疗前[(15.3±7.6)%]及使用紫杉醇前[(14.9±5.9)%]均显著升高(P0.01)。结论:相较于CEF方案,EC序贯P方案对术后乳腺癌患者的免疫功能影响较小。同时,紫杉醇能增加乳腺癌患者NK细胞比例,而不影响总T淋巴细胞及杀伤性T淋巴细胞比例,在保留早期乳腺癌患者抗肿瘤免疫功能方面具有优越性。
[Abstract] Background and purpose: Immunity function is one of the most profound factors in affecting the prognosis of breast cancer patients. Cytotoxic T lymphocytes counts in the peripheral blood and focal tumor tissue could indicate the overall survival time of these patients. On the other hand
adjuvant chemotherapy is also an important part in improving both the disease free survival and overall survival time of breast cancer patients. Selecting chemotherapy regime which is both able to kill all the tumor cells and reserve the immunity function to the greatest extent is of great importance in improving the survival rate of breast cancer patients. The aim of this study was to compare the effect of two chemotherapy regimens CEF (cyclophosphamide
epirubicin and fluorouracil) and EC followed by P (paclitaxel) on the peripheral blood lymphocytes in early stage breast cancer. Methods: The clinicopathological characteristics and peripheral blood lymphocyte parameters before and after chemotherapy of CEF or EC-P regimen were retrospectively analyzed in post-operate patients with early stage breast cancer during the period from Nov. 2012 to May 2013. The lymphocyte parameters included: total blood lymphocytes count
percentages of T lymphocytes
cytotoxic T lymphocytes
helper T lymphocytes
active T lymphocytes and nature killer (NK) cells. Results: Patients undertook EC-P regimen were those at comparably high risk (significant differences of clinical stage
tumor size
axillary lymph node status
estrogen/progestogen receptor and histological subtype were observed). There was no difference of lymphocyte parameters between these two groups before adjuvant chemotherapy. However
during the process of chemotherapy
peripheral blood lymphocytes counts decreased significantly after 4 and 5 cycles of chemotherapy of CEF regime (1 077±359/μL; 1 181±271/μL) compared with the level before chemotherapy (1 607±322/μL
P0.05). On the contrary
there was no significant difference of peripheral blood lymphocytes count before (1 746±576 /μL) and after 4 and 5 cycles of chemotherapy (1 500±312/μL; 1 623±468/μL) in EC-P group (P0.05). Percentage of active T lymphocyte increased significantly along with the chemotherapy in both groups (CEF group: 11.8±7.1 vs 23±9.3
P0.05; EC-P group: 11.8±5.8 vs 17.6±8.2
P0.05) (pre-chemotherapy vs after 5 cycles of chemotherapy). In EC-P group
the percentage of helper T lymphocyte (37.8±5.7) decreased significantly compared with the levels before chemotherapy (41.3±4.3) and before paclitaxel was undertaken (41.9±5.6
P0.05) and the percentage of NK cells (21.5±5.2) increased significantly compared with the levels before chemotherapy (15.3±7.6) and before paclitaxel was undertaken (14.9±5.9
P0.01) after one cycle of paclitaxel therapy. Conclusion:The effect of chemotherapy on peripheral blood lymphocyte is less profound in EC-P group compared to CEF group. Furthermore
paclitaxel can increase the NK cells without any effect to the levels of T lymphocytes and cytotoxic T lymphocyte. It is superior over other drug in conserving immune function in early stage breast cancer.
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