新辅助化疗后三阴性乳腺癌患者肿瘤浸润淋巴细胞亚群在残留肿瘤中的预后价值。

Prognostic value of tumor-infiltrating lymphocyte subtypes in residual tumors of patients with triple-negative breast cancer after neoadjuvant chemotherapy.

机构信息

Breast Disease Center, Peking University First Hospital, Beijing 100034, China.

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

出版信息

Chin Med J (Engl). 2020 Mar 5;133(5):552-560. doi: 10.1097/CM9.0000000000000656.

DOI:10.1097/CM9.0000000000000656

PMID:32044815

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7065871/

Abstract

BACKGROUND

After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC.

METHODS

Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics.

RESULTS

A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17-106 months). There was no significant correlation between the infiltrate density of CD4, CD8, CD20, and CD68 lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8-TILs (DFS: P = 0.018) and low CD20-TILs (OS: P = 0.042). Further analysis showed that patients with CD4/CD20 ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8/CD20 ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis.

CONCLUSIONS

Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

摘要

背景

新辅助化疗（NAC）后，乳腺癌患者非病理性完全缓解可从针对性辅助化疗中获益。然而，对于需要进行额外辅助化疗以获得最大获益的预后较差的患者，难以进行选择。本研究旨在探讨残留肿瘤（RT）中肿瘤浸润淋巴细胞（TILs）的亚群与新辅助化疗后三阴性乳腺癌（TNBC）的预后是否相关。

方法

回顾性分析 2008 年至 2014 年期间于北京大学第一医院乳腺疾病中心连续诊断的原发性 TNBC 患者的资料，入组新辅助化疗后 RT 中有肿瘤组织的病例。采用双重免疫组织化学染色观察 RT 中 TIL 亚群，并以每平方毫米的中位数 TIL 为界值，定义各亚群中高与低 TIL 密度。采用 Fisher 确切检验分析各亚组 TIL 密度与新辅助化疗后 RT 患者临床病理特征的关系。采用 Kaplan-Meier 法和对数秩检验分析无病生存（DFS）和总生存（OS）。

结果

本研究共纳入 37 例符合条件的患者，中位随访时间为 50 个月（17-106 个月）。CD4、CD8、CD20 和 CD68 淋巴细胞浸润密度与临床病理特征之间无显著相关性。高 CD4-TILs（DFS：P=0.005，OS：P=0.021）、高 CD8-TILs（DFS：P=0.018）和低 CD20-TILs（OS：P=0.042）患者的预后明显更好。进一步分析显示，CD4/CD20 比值大于 1（DFS：P=0.001，OS：P=0.002）或 CD8/CD20 比值大于 1（DFS：P=0.009，OS：P=0.022）的患者预后更好。