A-S Heimes1, K Madjar2, K Edlund3, M J Battista4, K Almstedt4, T Elger4, S Krajnak4, J Rahnenführer2, W Brenner4, A Hasenburg4, J G Hengstler3, M Schmidt4. 1. Department of Obstetrics and Gynecology, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany. anne-sophie.heimes@unimedizin-mainz.de. 2. Department of Statistics, TU Dortmund University, Dortmund, Germany. 3. Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU Dortmund, Dortmund, Germany. 4. Department of Obstetrics and Gynecology, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.
Abstract
BACKGROUND: The role of different subtypes of immune cells is still a matter of debate. METHODS: 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. RESULTS: 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). CONCLUSION: Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.
BACKGROUND: The role of different subtypes of immune cells is still a matter of debate. METHODS: 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 cancerpatients 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. RESULTS: 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). CONCLUSION: Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.
Authors: Cinzia Solinas; Soizic Garaud; Pushpamali De Silva; Anaïs Boisson; Gert Van den Eynden; Alexandre de Wind; Paolo Risso; Joel Rodrigues Vitória; François Richard; Edoardo Migliori; Grégory Noël; Hugues Duvillier; Ligia Craciun; Isabelle Veys; Ahmad Awada; Vincent Detours; Denis Larsimont; Martine Piccart-Gebhart; Karen Willard-Gallo Journal: Front Immunol Date: 2017-10-30 Impact factor: 7.561
Authors: Marcus Schmidt; Veronika Weyer-Elberich; Jan G Hengstler; Anne-Sophie Heimes; Katrin Almstedt; Aslihan Gerhold-Ay; Antje Lebrecht; Marco J Battista; Annette Hasenburg; Ugur Sahin; Konstantine T Kalogeras; Pirkko-Liisa Kellokumpu-Lehtinen; George Fountzilas; Ralph M Wirtz; Heikki Joensuu Journal: Breast Cancer Res Date: 2018-02-26 Impact factor: 6.466