乳腺癌新辅助化疗前后分子分型和免疫组化表达变化与疗效的相关性

Correlation between molecular typing and immunohistochemical expression changes of breast cancer before and after neoadjuvant chemotherapy and therapeutic efficacy

目的:分析乳腺癌新辅助化疗(NAC)前后分子分型和免疫组化(IHC)表达改变的情况,探讨新辅助治疗后IHC结果发生改变可能的相关因素。方法:回顾性收集2014年3月至2022年8月在我院接受NAC的共151例乳腺癌患者的临床、病例资料。新辅助所有患者均进行4~6周期的新辅助放化疗且行乳腺癌改良根治术或根治术。根据Miller-Payne分级为评估标准,分为pCR与非病理完全缓解(non-pCR)两个亚组。观察分析NAC后non-pCR组患者IHC指标雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(Her-2)、细胞增殖抗原(Ki-67)及分子分型出现改变的现象,采用χ^(2)检验分析新辅助化疗前后non-pCR组IHC指标及分子分型的差异性;采用皮尔逊相关系数检验IHC表达及分子分型在NAT后发生变化的情况。分析新辅助化疗患者pCR与临床病理特征间的关系,临床病理特征主要包括年龄、累及乳腺、病理类型、免疫组化标记物及分子分型的相关性。采用多因素Logistic回归分析来检验pCR相关的影响因素。结果:151例乳腺癌患者,Luminal A型6例,Luminal B型81例,Her-2过表达29例,三阴性35例。经NAC后,pCR患者占40.4%(61/151),non-pCR患者占59.6%(90/151)。90例non-pCR患者。病理学结果相对于治疗前,新辅助化疗后ER(阳性表达无变化,χ^(2)=0.000,P=1.000)、PR(阳性表达减少9例,χ^(2)=2.730,P=0.098)和Her-2(阳性表达减少3例,χ^(2)=0.284,P=0.594)差异无统计学意义(P>0.05),Ki-67高表达治疗后54例(60.0%)较治疗前83例(92.2%)明显下降,差异具有显著统计学意义(χ^(2)=25.697,P<0.001)。新辅助化疗pCR疗效与临床病理特征方面分析,ER状态(χ^(2)=16.130,P=0.000)、PR状态(χ^(2)=18.881,P=0.000)、 Her-2状态(χ^(2)=25.414,P=0.000)、分子分型(χ^(2)=17.365,P=0.001)与新辅助化疗pCR效果相关,多因素回归分析在校正其他变量后,ER阴性(P=0.023,OR=0.141, 95%CI=0.026~0.760)和Her-2阳性(P=0.000,OR=10.674,95%CI=2.911~39.138)可作为新辅助化疗pCR效果的预测因子。结论:乳腺癌NAC能够降低Ki-67的表达水平,ER阴性和Her-2阳性与乳腺癌NAC病理缓解有关,对NAC判断预后具有一定的指导作用。

Objective:To analyze the changes in molecular typing and immunohistochemical(IHC)expression of breast cancer before and after neoadjuvant chemotherapy(NAC),and to explore the possible related factors for the changes in IHC results after neoadjuvant therapy.Methods:Clinical and case data of 151 patients with breast cancer who received NAC in our hospital from March 2014 to August 2022 were retrospectively collected.All patients underwent 4~6 cycles of neoadjuvant chemoradiotherapy and modified radical mastectomy or radical mastectomy.According to the Miller-Payne grading,patients were divided into pCR group and non-pathologic complete response(non-pCR)group.The changes of IHC indexes,such as estrogen receptor(ER),progesterone receptor(PR),human epidermal growth factor receptor 2(Her-2),cell proliferation antigen(Ki-67)and molecular typing of patients in the non-pCR group after NAC were observed.χ^(2) test was used to analyze the differences of IHC indexes and molecular typing in the non-pCR group before and after neoadjuvant chemotherapy.Pearson correlation coefficient was used to examine the changes of IHC expression and molecular typing after NAT.The relationship between pCR and clinicopathological features of neoadjuvant chemotherapy patients was analyzed.The clinicopathological features mainly included age,involvement of mammary gland,pathological type,immunohistochemical markers and molecular typing.Multivariate Logistic regression analysis was used to examine the PCR-related influencing factors.Results:There were 151 patients with breast cancer,6 with Luminal A,81 with Luminal B,29 with Her-2 overexpression,and 35 with triple-negative.After NAC,pCR patients accounted for 40.4%(61/151)and non-pCR patients accounted for 59.6%(90/151).In 90 non-pCR patients,compared with before treatment,ER(positive expression did not change,χ^(2)=0.000,P=1.000),PR(positive expression decreased in 9 cases,χ^(2)=2.730,P=0.098)and Her-2(positive expression decreased in 3 cases,χ^(2)=0.284,P=0.594)after neoadjuvant chemotherapy were not significantly difference(P>0.05).Ki-67 high expression was significantly decreased in 54 cases(60.0%)after treatment compared with 83 cases(92.2%)before treatment,and the difference was statistically significant(χ^(2)=25.697,P<0.001).ER status(χ^(2)=16.130,P=0.000),PR status(χ^(2)=18.881,P=0.000),Her-2 status(χ^(2)=25.414,P=0.000),molecular classification(χ^(2)=17.365,P=0.001)were correlated with the pCR effect of neoadjuvant chemotherapy.Multivariate regression analysis showed negative ER(P=0.023,OR=0.141,95%CI=0.026~0.760)and positive Her-2(P=0.000,OR=10.674,95%CI=2.911~39.138)after adjusting for other variables can be used as predictors of pCR effect of neoadjuvant chemotherapy.Conclusion:NAC in breast cancer can reduce the expression level of Ki-67,and negative ER and positive Her-2 are related to pathological remission of breast cancer NAC,which has a certain guiding role in judging the prognosis of NAC.