Breast Cancer Research and Treatment

, Volume 165, Issue 2, pp 293–300 | Cite as

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

  • A.-S. Heimes
  • K. Madjar
  • K. Edlund
  • M. J. Battista
  • K. Almstedt
  • T. Elger
  • S. Krajnak
  • J. Rahnenführer
  • W. Brenner
  • A. Hasenburg
  • J. G. Hengstler
  • M. Schmidt
Preclinical study



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.


TILs Antitumor immunity Immune signatures 



No funding was received.

Compliance with ethical standards

Competing interest

The authors have no conflict of interest.

Ethics approval

The study was approved by the Research Ethics Committee of the University Medical Centre Mainz, Germany. Informed consent was obtained from all patients and all clinical investigations were conducted according to the ethical and legal standards.

Supplementary material

10549_2017_4327_MOESM1_ESM.doc (68 kb)
Supplementary material 1 (DOC 67 kb)


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • A.-S. Heimes
    • 1
  • K. Madjar
    • 2
  • K. Edlund
    • 3
  • M. J. Battista
    • 1
  • K. Almstedt
    • 1
  • T. Elger
    • 1
  • S. Krajnak
    • 1
  • J. Rahnenführer
    • 2
  • W. Brenner
    • 1
  • A. Hasenburg
    • 1
  • J. G. Hengstler
    • 3
  • M. Schmidt
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity Medical CenterMainzGermany
  2. 2.Department of StatisticsTU Dortmund UniversityDortmundGermany
  3. 3.Leibniz Research Centre for Working Environment and Human Factors (IfADo) at TU DortmundDortmundGermany

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