Abstract

Abstract Triple negative breast cancer (TNBC) are defined by the lack of expression of ER, PR and HER2 receptors and characterized by an aggressive clinical history and poor outcome. Considering that these tumors do not present a good response to the available adjuvant target therapies (hormonal and HER-2 based therapies), there is a critical need to identify new markers to improve treatment options for these patients. The use of genome-wide methodologies is a progress towards this direction, through the identification of biomarkers that can be translated into novel target-based therapies. We report the genomic profiling performed by array-CGH (Agilent 4x44K) in 33 cases of TNBC obtained from Hospital N.S. das Gracas and Hospital das Clinicas (UFPR), Curitiba, South of Brazil. Copy number alterations in potentially therapeutic target genes for TNBC (involved in the PI3K-AKT pathway) were evaluated by TaqMan copy number assay (Applied Biosystems). The data was correlated with pathological parameters from the patients. Copy number changes were observed by array-CGH in 87% (25/30) of the TNBC cases analyzed, with a median of 9.97+12.37 alterations per case. Based on this value, the samples were divided into two categories (>10 and <10 alterations); no significantly difference was observed between these categories and tumor size (t=1.74;P>0.05) or the presence of lymph node (LN) metastasis (≥2=1.8;P>0.10) and tumor grade (≥2=1.18;P>0.20). Although a high degree of molecular heterogeneity was observed, amplification on 8q was observed in 50% (15/30) of the cases, mostly involving 8q24.3. Tumor size was not significantly different among the cases with or without 8q amplification (t=1,88; P>0.20). These cases were also equally distributed in relation to LN metastasis (≥2=2.67;P>0.10) and tumor grade (≥2=0.5;P>0.50). Finally, alterations in at least one gene involved in the PIK3/AKT pathway were observed in 88% (29/33) of the cases and in more than three genes in 45% (13/29) of the cases. PIK3CA and PTEN were the most frequently altered genes: gained and lost in 42% and 40% of the cases respectively. AKT2, AKT1, and FGFR2 genes were observed gained in 24%, 21% and 21% of the cases respectively. Alterations in those genes were also not significantly correlated with tumor size (t=0.95; P>0.30), LN metastasis (≥2=0.16; P>0.50) and tumor grade (≥2=3.23; P>0.05). Our results indicate a high level of DNA copy number changes in TNBC cases, involving mostly chromosome 8q. Alterations on genes involved in the PIK3/AKT pathway were also common; immunohistochemistry analyses are in progress to evaluate those alterations at the expression level. No significant correlations were observed among the genomic alterations and the pathological parameters from the patients. This lack of correlation can be due to the limited sample size or can indicate that in our set of TNBC cases tumor size, LN metastasis and tumor grade are not associated with an elevated genomic instability. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5100. doi:1538-7445.AM2012-5100

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