Heimes A-S, Madjar K, Edlund K, Battista M J, Almstedt K, Elger T, Krajnak S, Rahnenführer J, Brenner W, Hasenburg A, Hengstler J G, Schmidt M
Department of Obstetrics and Gynecology, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.
Department of Statistics, TU Dortmund University, Dortmund, Germany.
Breast Cancer Res Treat. 2017 Sep;165(2):293-300. doi: 10.1007/s10549-017-4327-0. Epub 2017 Jun 5.
The role of different subtypes of immune cells is still a matter of debate.
We compared the prognostic relevance for metastasis-free survival (MFS) of a B-cell signature (BS), a T-cell signature (TS), and an immune checkpoint signature (CPS) in node-negative breast cancer (BC) using mRNA expression. Microarray-based gene-expression data were analyzed in six previously published cohorts of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic relevance of the individual immune markers was assessed using univariate analysis. The amount of independent prognostic information provided by each immune signature was then compared using a likelihood ratio statistic in the whole cohort as well as in different molecular subtypes.
Univariate Cox regression in the whole cohort revealed prognostic significance of CD4 (HR 0.66, CI 0.50-0.87, p = 0.004), CXCL13 (HR 0.86, CI 0.81-0.92, p < 0.001), CD20 (HR 0.76, CI 0.64-0.89, p = 0.001), IgκC (HR 0.81, CI 0.75-0.88, p < 0.001), and CTLA-4 (HR 0.67, CI 0.46-0.97, p = 0.032). Multivariate analyses of the immune signatures showed that both TS (p < 0.001) and BS (p < 0.001) showed a significant prognostic information in the whole cohort. After accounting for clinical-pathological variables, TS (p < 0.001), BS (p < 0.05), and CPS (p < 0.05) had an independent effect for MFS. In subgroup analyses, the prognostic effect of immune cells was most pronounced in HER2+ BC: BS as well as TS showed a strong association with MFS when included first in the model (p < 0.001).
Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.
不同亚型免疫细胞的作用仍存在争议。
我们使用mRNA表达比较了B细胞特征（BS）、T细胞特征（TS）和免疫检查点特征（CPS）对淋巴结阴性乳腺癌（BC）无转移生存期（MFS）的预后相关性。在六个先前发表的未接受辅助治疗的淋巴结阴性乳腺癌患者队列（n = 824）中分析基于微阵列的基因表达数据。使用单变量分析评估各个免疫标志物的预后相关性。然后在整个队列以及不同分子亚型中使用似然比统计量比较每个免疫特征提供的独立预后信息的量。
整个队列中的单变量Cox回归显示CD4（HR 0.66，CI 0.50 - 0.87，p = 0.004）、CXCL13（HR 0.86，CI 0.81 - 0.92，p < 0.001）、CD20（HR 0.76，CI 0.64 - 0.89，p = 0.001）、IgκC（HR 0.81，CI 0.75 - 0.88，p < 0.001）和CTLA - 4（HR 0.67，CI 0.46 - 0.97，p = 0.032）具有预后意义。免疫特征的多变量分析表明，TS（p < 0.001）和BS（p < 0.001）在整个队列中均显示出显著的预后信息。在考虑临床病理变量后，TS（p < 0.001）、BS（p < 0.05）和CPS（p < 0.05）对MFS具有独立影响。在亚组分析中，免疫细胞的预后作用在HER2 + BC中最为明显：当首先纳入模型时，BS以及TS与MFS显示出强烈关联（p < 0.001）。
在淋巴结阴性乳腺癌中，免疫特征比临床病理变量提供亚型特异性的额外预后信息。
