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RESEARCH PRODUCT

Abstract P2-05-04: Gene expression associated with poor prognosis of young TNBC patients

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Abstract Background: Among TNBC patients those of very young age (<40 years) display a significantly worse prognosis (Liedtke et al. 2013 Breast Cancer Res Treat). We verified this result in 1161 TNBC samples with full Affymetrix gene expression data of which 845 patients had both detailed age and follow up information. Materials and Methods: We split the full sample set into a finding cohort of 394 TNBC and a validation cohort of 767 TNBC encompassing 309 and 536 samples, respectively, with both age and follow up data. We then used significance analysis of microarrays (SAM) in the finding cohort to look for genes whose expression is associated with young age (<40 years). Identified genes were analyzed for their correlations to known metagenes characteristic for different TNBC subtypes. Subsequently the whole analysis was repeated in the validation cohort. Results: We identified 98 and 222 probesets by SAM in the finding and validation cohort, respectively. Only a subset of identical probesets (19.4%) was re-identified in the validation. However, the gene lists were similarily enriched for correlations to specific metagenes and the respective TNBC subtypes. We found that young age among TNBC is positively correlated with increased proliferation and a basal-like subtype, but negatively correlated with the molecular apocrine phenotype and the claudin-low subtype. We also observed a negative correlation of young age with stromal enrichment and EMT but no difference in lymphocyte infiltration as judged by specific metagenes. However, despite that TNBC of patients <40 years have a poor prognosis (P=0.006) and are clearly enriched in basal-like subtype (70.7% vs 55.3%; P=0.001), still basal-like TNBC do not differ from non-basal-like TNBC in prognosis. Moreover, even within the group of basal-like TNBC the prognostic effect of age<40 was still observed (P=0.008). Interestingly, the changes in expression of single genes and metagenes were observed over a wide age range of 35-85 years. In contrast the difference in prognosis was markedly pronounced at the 40 year age limit. Thus, potential critical differences in gene expression associated with poor prognosis of TNBC <40 years seem to be concealed by many age-associated changes without prognostic value. Citation Format: Thomas Karn, Lajos Pusztai, Cornelia Liedtke, Giampaolo Bianchini, Balazs Györffy, Christos Hatzis, Achim Rody, Volkmar Müller, Marcus Schmidt, Uwe Holtrich, Sven Becker. Gene expression associated with poor prognosis of young TNBC patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-04.