da Silva Jesse Lopes, de Albuquerque Lucas Zanetti, Rodrigues Fabiana Resende, de Mesquita Guilherme Gomes, Fernandes Priscila Valverde, Thuler Luiz Claudio Santos, de Melo Andreia Cristina
Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
Division of Pathology, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
Front Oncol. 2021 Nov 9;11:636716. doi: 10.3389/fonc.2021.636716. eCollection 2021.
This study aimed to examine the prevalence and prognostic role of tumor microenvironment (TME) in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) through immunohistochemical characterization.
The internal database of the Brazilian National Cancer Institute for women diagnosed with TNBC who underwent NACT and thereafter curative surgery between January 2010 and December 2014 was queried out. Core biopsy specimens and tissue microarrays containing surgical samples of TNBC from 171 and 134 women, respectively, were assessed by immunohistochemistry for CD3, CD4, CD8, CD14, CD56, CD68, CD117, FOXP3, PD-1, PD-L1, and PD-L2. Immune cell profiles were analyzed and correlated with response and survival.
Mean age was 50.5 years, and most cases were clinical stage III [143 cases (83.6%)]. According to the multivariate analysis, only Ki67 and clinical stage significantly influenced the pattern of response to systemic treatment ( = 0.019 and = 0.033, respectively). None of the pre-NACT IHC markers showed a significant association with event-free survival (EFS) or overall survival (OS). As for post-NACT markers, patients with high CD14 had significantly shorter EFS ( = 0.015), while patients with high CD3 ( = 0.025), CD4 ( = 0.025), CD8 ( = 0.030), CD14 ( = 0.015), FOXP3 ( = 0.005), high CD4/FOXP3 ( = 0.034), and CD8/FOXP3 ( = 0.008) showed longer EFS. Only high post-NACT CD4 showed significantly influenced OS ( = 0.038).
The present study demonstrated that the post-NACT TIL subtype can be a determining factor in the prognosis of patients with TNBC.
本研究旨在通过免疫组化特征分析，探讨肿瘤微环境（TME）在新辅助化疗（NACT）后三阴性乳腺癌（TNBC）中的患病率及预后作用。
查询巴西国家癌症研究所的内部数据库，找出2010年1月至2014年12月期间诊断为TNBC并接受NACT及后续根治性手术的女性患者。分别对171例和134例女性患者的TNBC核心活检标本和包含手术样本的组织芯片进行免疫组化检测，检测指标包括CD3、CD4、CD8、CD14、CD56、CD68、CD117、FOXP3、PD-1、PD-L1和PD-L2。分析免疫细胞谱，并与反应和生存情况进行关联。
平均年龄为50.5岁，大多数病例为临床III期[143例（83.6%）]。根据多因素分析，只有Ki67和临床分期对全身治疗反应模式有显著影响（分别为=0.019和=0.033）。新辅助化疗前的免疫组化标志物均与无事件生存期（EFS）或总生存期（OS）无显著关联。至于新辅助化疗后的标志物，CD14高表达的患者EFS显著缩短（=0.015），而CD3（=0.025）、CD4（=0.025）、CD8（=0.030）、CD14（=0.015）、FOXP3（=0.005）、CD4/FOXP3高表达（=0.034）和CD8/FOXP3高表达（=0.008）的患者EFS较长。只有新辅助化疗后CD4高表达对OS有显著影响（=0.038）。
本研究表明，新辅助化疗后的肿瘤浸润淋巴细胞（TIL）亚型可能是TNBC患者预后的决定因素。
