TY  - JOUR
A1  - Karn, Thomas
A1  - Pusztai, Lajos
A1  - Holtrich, Uwe
A1  - Iwamoto, Takayuki
A1  - Shiang, Christine Y.
A1  - Schmidt, Marcus
A1  - Müller, Volkmar
A1  - Solbach, Christine
A1  - Gätje, Regine
A1  - Hanker, Lars
A1  - Ahr, André
A1  - Liedtke, Cornelia
A1  - Ruckhäberle, Eugen
A1  - Kaufmann, Manfred
A1  - Rody, Achim
T1  - Homogeneous datasets of triple negative breast cancers enable the identification of novel prognostic and predictive signatures
T2  - PLoS One
N2  - Background: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC) cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes.

Methodology/Principal Findings: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases).

Conclusions/Significance: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets) and a smaller (n = 26 probesets) prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature) was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71–9.48; P = 0.001) and 4.08 (95% CI 1.79–9.28; P = 0.001), respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588) to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22835
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-228359
SN  - 1932-6203
VL  - 6
IS  - 12: e28403
PB  - PLoS
CY  - Lawrence, Kan.
ER  -