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Breast Cancer Research
Published in: Breast Cancer Research 5/2011

Open Access 01-10-2011 | Research article

A clinically relevant gene signature in triple negative and basal-like breast cancer

Authors: Achim Rody, Thomas Karn, Cornelia Liedtke, Lajos Pusztai, Eugen Ruckhaeberle, Lars Hanker, Regine Gaetje, Christine Solbach, Andre Ahr, Dirk Metzler, Marcus Schmidt, Volkmar Müller, Uwe Holtrich, Manfred Kaufmann

Published in: Breast Cancer Research | Issue 5/2011

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Abstract

Introduction

Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease.

Methods

We assembled Affymetrix gene expression data for 579 TNBC and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n = 394 cases for discovery and n = 185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations, including immune cells, blood, adipocytes, stroma, angiogenesis and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed, including routine clinical and pathological variables.

Results

Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (hazard ratio (HR) 0.37, 95% CI 0.22 to 0.61; P < 0.001) and was the only significant predictor in multivariate analysis including routine clinicopathological variables.

Conclusions

We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease.
Appendix
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Metadata
Title
A clinically relevant gene signature in triple negative and basal-like breast cancer
Authors
Achim Rody
Thomas Karn
Cornelia Liedtke
Lajos Pusztai
Eugen Ruckhaeberle
Lars Hanker
Regine Gaetje
Christine Solbach
Andre Ahr
Dirk Metzler
Marcus Schmidt
Volkmar Müller
Uwe Holtrich
Manfred Kaufmann
Publication date
01-10-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3035

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