【作者】 陈颖；

【导师】 姜义；

【作者基本信息】 吉林大学 ， 临床医学硕士（外科学）（专业学位）， 2020， 硕士

【摘要】 背景:近年来,新辅助化疗(neoadjuvant chemotherapy,NAC)成为了乳腺癌的治疗过程中的重要方法。化疗相关性中性粒细胞减少(chemotherapy-induced neutropenia,CIN)是化疗常见的不良反应,但同时CIN从一定程度上反应了化疗药物的有效性以及患者对于药物的敏感性。有回顾性研究发现在乳腺癌辅助化疗过程中出现CIN的患者有更好的生存优势,也有研究发现乳腺癌NAC过程中有相似的现象。在NAC过程中,早期的疗效评估会影响治疗策略的制定。CIN的出现是否与NAC早期疗效较好有关,化疗药物对于中性粒细胞的杀伤是否和肿瘤细胞的杀伤相关,是否可以成为一个乳腺癌NAC期间预测化疗效果的因子有待研究。目的:探讨CIN与乳腺癌NAC疗效之间的相关性,同时分析影响乳腺癌NAC疗效的相关因素。方法:回顾性分析自2015年3月至2019年12月于吉林大学第二医院乳腺外科进行NAC后行手术治疗的乳腺癌患者164例。收集包括年龄、绝经情况、BMI、化疗评估的影像结果、化疗期间中性粒细胞计数结果、术前穿刺及术后的病理结果及免疫组化结果(包括ER、PgR、HER2、Ki-67等指标)。中性粒细胞计数<1.5×10~9/L作为CIN标准,以化疗过程中的影像评估结果和手术后的病理完全缓解(pathologic complete response,pCR)作为化疗疗效的指标,分析CIN与NAC疗效的相关性及NAC疗效的相关因素。结果:1.单因素分析结果显示,临床影像评估结果在Ki-67表达水平上有统计学差异(P=0.024),Ki-67高表达与临床影像评估有效有关。多因素分析时,Ki-67高表达是影像评估有效的独立相关因素(OR=2.26,P=0.026)。2.单因素分析结果显示,pCR在ER状态(P=0.000)、分子分型(P=0.022)、NAC前淋巴结状态(P=0.000)及影像评估结果(P=0.003)上有统计学差异。Luminal A型、Luminal B型、ERBB2+型和Basal-like型的pCR率分别为9%、7%、20%和27%,差异有统计学意义,ER低表达、NAC前淋巴结阴性和影像评估结果有效的患者pCR率更高。其中ER低表达(OR=10.54,P=0.003)、NAC淋巴结阴性(OR=3.68,P=0.033)和临床影像评价有效(OR=13.58,P=0.013)经过多因素分析是pCR的独立相关因素。3.在未联用新辅助靶向治疗的单纯NAC的组别分析中,影像评估结果在CIN结果上有统计学差异(P=0.008),出现CIN的患者与影像评估有效有关。多因素分析时,NAC期间出现CIN是影像评估有效的独立相关因素(OR=2.23,P=0.013)。4.CIN是否出现在PgR的状态方面有统计学差异(P=0.019),PgR低表达与CIN有关。多因素分析时,PgR低表达是NAC期间出现CIN一个独立相关因素(OR=2.723,P=0.022)。结论:1.在未联用新辅助靶向治疗的单纯NAC的患者中,化疗期间出现CIN与NAC疗效有关,出现CIN与临床影像评估有效有关。2.ER、Ki-67、NAC前淋巴结状态与NAC疗效有关。ER低表达、Ki-67高表达和NAC前淋巴结阴性与NAC疗效好有关。3.PgR是NAC期间出现CIN一个独立相关因素,PgR低表达的患者更容易出现CIN。更多还原

【Abstract】 Background: Neoadjuvant chemotherapy(NAC)has been an important therapy in the treatment of breast cancer in recent years for the advantages of downstaging the tumor for surgery and increasing the probability of breast-conserving surgery and gather information about sensitivity of chemotherapeutic drugs in the body.Chemotherapyinduced neutropenia(CIN)is a common adverse reaction of chemotherapy,but at the meantime CIN could reflect partly the effectiveness of chemical drugs and drug sensitivity in patients.Some retrospective studies show that patients with CIN in breast cancer during adjuvant chemotherapy have a better survival,while other studies show similar results during neoadjuvant chemotherapy.NAC treatment strategies are affected by evaluation of chemotherapeutic drugs.Whether CIN is related to the better efficacy of neoadjuvant chemotherapy and whether it can be a factor to predict the efficacy of chemotherapy during neoadjuvant chemotherapy remains to be studied.Objective: To study the correlation between CIN and the efficacy of NAC in breast cancer,and to find the factors related to the efficacy of NAC in breast cancer.Methods: Retrospective analysis was performed on 164 breast cancer patients who underwent NAC and followed operative in department of breast disease of the second hospital of Jilin university from March 2015 to December 2019.Patients data including age,menopausal status,BMI,chemotherapy evaluation,blood routine results,imaging results,preoperative puncture and postoperative pathological results,and immunohistochemical results(including ER,Pg R,HER2,Ki-67 and other indicators)were collected.CIN was defined as positive when the neutrophil count was less than <1.5×109/L.The imaging evaluation results during chemotherapy and pathologic complete response(p CR)after surgery were used as indicators of the efficacy of chemotherapy to analyze the correlation between CIN and NAC efficacy and the factors related to the efficacy of NAC.Results: 1.The results of univariate analysis showed the high Ki-67 expression was related to the effectiveness of clinical imaging evaluation(P=0.024).In multivariate analysis,the high Ki-67 expression was an effective independent correlation factor for imaging evaluation(OR=2.26,P=0.026).2.The results of univariate analysis showed that p CR showed statistical differences in ER(P=0.000),molecular type(P=0.022),lymph node status before NAC(P=0.000)and imaging evaluation results(P=0.003).The p CR rates of Luminal A,Luminal B,ERBB2+ and Basal like were 9%,7%,20% and 27% respectively,in which the differences were statistically significant.And the low expression of ER,negative lymph nodes before NAC and effective clinical imaging evaluation were related to the p CR.Low ER expression(OR=10.54,P=0.003),lymph node negative before NAC(OR=3.68,P=0.033)and clinical imaging evaluation of effective(OR=13.58,P=0.013)were independent correlation factors of p CR in multivariate analysis.3.In the group analysis of only NAC without neoadjuvant targeted therapy,the imaging evaluation results showed statistical differences in the presence of CIN(P=0.008).CIN in patients was associated with the effectiveness of the imaging assessment.In multivariate analysis,CIN is an effective independent correlation factor for image evaluation(OR=2.23,P=0.013).4.There was a statistical difference in the presence of CIN in the state of Pg R(P=0.019),and the low expression of Pg R was related to CIN.In multivariate analysis,the low Pg R expression was an independent factor related to CIN during NAC(OR=2.723,P=0.022).Conclusion:1.In patients with only NAC without neoadjuvant targeted therapy,the presence of CIN during chemotherapy was related to the efficacy of NAC.2.ER,Ki-67 and lymph node status before NAC were related to the efficacy of NAC.Patients with low ER expression,high Ki-67 expression and negative lymph nodes before NAC were related to the efficacy of NAC.3.Pg R is an independent related factor for CIN during NAC,and patients with low Pg R expression are more likely to develop CIN.更多还原