Open Access Highly Accessed Research article

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

Achim Rody1, Thomas Karn1*, Cornelia Liedtke2, Lajos Pusztai3, Eugen Ruckhaeberle1, Lars Hanker1, Regine Gaetje1, Christine Solbach1, Andre Ahr1, Dirk Metzler4, Marcus Schmidt5, Volkmar Müller6, Uwe Holtrich1 and Manfred Kaufmann1

Author Affiliations

1 Department of Obstetrics and Gynecology, J. W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany

2 Department of Obstetrics and Gynecology, University of Muenster, Albert-Schweitzer Straße 33, 48149, Muenster, Germany

3 Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA

4 Department of Biology II, Ludwig-Maximilians-University Munich, Grosshaderner Str. 2, Planegg-Martinsried, 82152, Germany

5 Department of Obstetrics and Gynecology, J. Gutenberg-University, Langenbeckstr. 1, Mainz, 55131, Germany

6 Department of Obstetrics and Gynecology, University of Hamburg, Martinistrasse 52, Hamburg, 20246, Germany

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Breast Cancer Research 2011, 13:R97  doi:10.1186/bcr3035

Published: 6 October 2011

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.