新辅助化疗对浸润性乳腺癌分子标志物及分子分型的影响

Research of relationship between the change of molecular marker of breast cancer after neoadjuvant chemotherapy and therapeutic effect

目的研究乳腺癌新辅助化疗(NAC)(蒽环类联合紫衫类)过程中,雌激素受体(ER)、孕激素受体(PR)、HER2状态和Ki67值的变化,以及这些变化是否会对分子分型产生影响。方法回顾性分析从2011年11月到2015年6月期间在军事医学科学院附属医院行蒽环联合紫衫类NAC的137例浸润性乳腺癌患者。通过免疫组织化学方法测定NAC前后组织中ER、PR、HER2以及Ki67,并分为:Luminal A、Luminal B、三阴性和HER2阳性4种分子亚型。NAC前后分子标志物和分子分型的变化采用χ~2检验或用Fisher确切概率法检验,并用Kappa检验对新辅助化疗前后的分子标志物及分子分型进行一致性检验。结果 NAC前后ER、PR、HER2、Ki67的一致率分别为88.32%、83.21%、94.16%和75.91%。ER、PR、HER2在NAC前后变化差异均无统计学意义(P值均大于0.05)。在NAC后Ki67值平均数从35.75%降到了19.12%(P<0.05)。除性激素受体(HR)阳性,HER2阴性型的肿瘤之外,其余病例的分子分型在NAC前后的结果一致(P=0.488)。NAC前后分子分型的一致率为57.66%,Kappa值=0.4020。结论 NAC会使浸润性乳腺癌Ki67的表达下降,并会影响HR阳性、HER2阴性型肿瘤的分子分型。

Objective To research whether the changes of estrogen receptor(ER),progesterone receptor(PR),HER2 associate with the efficacy,during the course of neoadjuvant chemotherapy(NAC)(anthracycline and docetaxel),and to research whether these changes will affect the molecular subtypes.Methods One hundred and thirty seven cases of patients given NAC(anthracycline and docetaxel) were retrospectively analyzed from November 2011 to June 2015 in the Affiliated Hospital of Academy of Military Medical Sciences. ER,PR,HER2 and Ki67 expression were tested by immunohistochemistry. According to immunohistochemistry results,the cases were divided into 4 molecular subtypes: Luminal A,Luminal B,triple negative and HER2 positive. Changes of ER,PR,HER2 and Ki67 expression and molecular subtypes after neoadjuvant chemotherapy were tested by Chi-square test and Fisher' s exact test,and Kappa test was used to test the consistency of molecular markers and molecular subtypes before and after NAC. Results Concordance rate of ER,PR,HER2 and Ki67 were 88. 32%,83. 21%,94. 16% and 75. 91 respectively.There was no significant difference in ER,PR and HER2 before and after NAC(P values were all more than0. 05). Ki67 average value had fallen from 35. 75% to 19. 12% after NAC(P < 0. 05). Molecular subtypes would haven not been changed after NAC,except for cases with Hormone receptors(HR) positive and HER2negative(P = 0. 488). Concordance rate of molecular subtypes between pre-NAC biopsies and post-NAC specimens was 57. 66%(Kappa = 0. 4020). Conclusion NAC leads to a decrease of Ki67 value in invasive breast cancer cases,and makes an effect on tumors with molecular subtype of HR +,HER2-.