Subtype-specific prognostic impact of different immune signatures in node-negative breast cancer.

Abstract

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.