Abstract 1727: Correlation between BRCA1 and LMO4 mRNA expression levels in Erlotinib-treated non small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations

Abstract

Abstract Background Advanced NSCLC p harboring EGFR mutations show impressive progression-free survival (PFS) when treated with erlotinib. However, presence of EGFR mutations only imperfectly predicts outcome. We demonstrated that co-existence of the EGFR T790M pretreatment mutation was detected in one-third of p and, in conjunction with elevated BRCA1 mRNA levels, dramatically influenced PFS to erlotinib. Though this model is a breakthrough in outcome of EGFR-mutated NSCLC p treated with TKIs, we choose to analyze the impact of CTIP and LMO4 gene expression levels on p outcome and their correlation with BRCA1. CtIP binds to BRCA1 and LMO4 forming a complex. LMO4 is a negative regulator of BRCA1 function in sporadic breast cancers. Methods mRNA expression of LMO4 and CTIP was examined by RT-PCR in pretreatment tumor biopsies of 72 NSCLC p with EGFR mutations treated with erlotinib. Expression levels were correlated with outcome to erlotinib and BRCA1 expression levels. Results BRCA1 significantly correlated with CtIP (r=0.31;P=0.01) and LMO4 (r=0.32;P=0.02). There was no correlation between CtIP and LMO4 (r=0.09;P=0.49).PFS was not reached for p with high levels of LMO4 vs 13 months for p with low levels (P=0.006). Overall survival (OS) was not reached for p with high levels of LMO4 vs 29 months for p with low levels (P=0.10). Expression levels of CtIP did not correlate with PFS and OS. PFS was not reached for p with low levels of BRCA1 and high levels of LMO4 vs 19 months for p with low levels of both genes (P=0.04). PFS was 8 months for p with high levels of BRCA1 and low levels of LMO4 vs 18 months for p with high levels of both genes (P=0.03). Conclusions BRCA1 and LMO4 mRNA levels examined by RT-PCR could predict PFS to erlotinib in p with EGFR mutations and could be useful for development of new therapeutic strategies. 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 1727. doi:1538-7445.AM2012-1727