TY  - JOUR
A1  - Rody, Achim
A1  - Karn, Thomas
A1  - Liedtke, Cornelia
A1  - Pusztai, Lajos
A1  - Ruckhäberle, Eugen
A1  - Hanker, Lars
A1  - Gätje, Regine
A1  - Solbach, Christine
A1  - Ahr, André
A1  - Metzler, Dirk
A1  - Schmidt, Marcus
A1  - Müller, Volkmar
A1  - Holtrich, Uwe
A1  - Kaufmann, Manfred
T1  - A clinically relevant gene signature in triple negative and basal-like breast cancer
T2  - Breast cancer research
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27598
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-275983
SN  - 1465-5411
SN  - 1465-542X
N1  - © 2011 Rody et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 13
IS  - 5, Art. R97
SP  - 1
EP  - 12
PB  - BioMed Central
CY  - London
ER  -