+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations



Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations



Clinical Cancer Research 17(5): 1160-1168



Advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (deletion in exon 19 or L858R) show an impressive progression-free survival of 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. We hypothesized that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways. We assessed the T790M mutation in pretreatment diagnostic specimens from 129 erlotinib-treated advanced NSCLC patients with EGFR mutations. The expression of eight genes and two proteins involved in DNA repair and four receptor tyrosine kinases was also examined. The EGFR T790M mutation was observed in 45 of 129 patients (35%). Progression-free survival was 12 months in patients with and 18 months in patients without the T790M mutation (P = 0.05). Progression-free survival was 27 months in patients with low BRCA1 mRNA levels, 18 months in those with intermediate levels, and 10 months in those with high levels (P = 0.02). In the multivariate analysis, the presence of the T790M mutation (HR, 4.35; P = 0.001), intermediate BRCA1 levels (HR, 8.19; P < 0.0001), and high BRCA1 levels (HR, 8.46; P < 0.0001) emerged as markers of shorter progression-free survival. Low BRCA1 levels neutralized the negative effect of the T790M mutation and were associated with longer progression-free survival to erlotinib. We advocate baseline assessment of the T790M mutation and BRCA1 expression to predict outcome and provide alternative individualized treatment to patients based on T790M mutations and BRCA1 expression.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 055147756

Download citation: RISBibTeXText

PMID: 21233402

DOI: 10.1158/1078-0432.ccr-10-2158


Related references

Clinical outcomes and secondary epidermal growth factor receptor (EGFR) T790M mutation among first-line gefitinib, erlotinib and afatinib-treated non-small cell lung cancer patients with activating EGFR mutations. International Journal of Cancer 144(11): 2887-2896, 2019

BRCA1, LMO4, and CtIP mRNA expression in erlotinib-treated non-small-cell lung cancer patients with EGFR mutations. Journal of Thoracic Oncology 8(3): 295-300, 2013

Heterogeneous resistance mechanisms in an EGFR exon 19-mutated non-small cell lung cancer patient treated with erlotinib: Persistent FGFR3-mutation, localized transformation to EGFR-mutated SCLC, and acquired T790M EGFR-mutation. Lung Cancer 113: 14-17, 2017

The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR-T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations. Bmc Cancer 18(1): 1241, 2018

Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non-Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR. Clinical Cancer Research 21(15): 3552-3560, 2015

The prognostic role of pretreatment epidermal growth factor receptor T790M mutation in advanced non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. Oncotarget 8(31): 50941-50948, 2017

Phase II study of erlotinib plus tivantinib (ARQ 197) in patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer just after progression on EGFR-TKI, gefitinib or erlotinib. Esmo Open 1(4): E000063, 2016

The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial. Clinical Cancer Research 20(7): 2001-2010, 2014

134O_PR: Plasma ctDNA analysis for detection of EGFR T790M mutation in patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (aNSCLC). Journal of Thoracic Oncology 11(4 Suppl.): S153-S154, 2016

The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncotarget 7(32): 51311-51319, 2016

Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. Journal of Clinical Oncology 30(4): 433-440, 2012

Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naïve patients with non-small cell lung cancer harboring EGFR mutations. Oncotarget 8(40): 68123-68130, 2017

Osimertinib for advanced non-small cell lung cancer harboring EGFR mutation exon 20 T790M, acquired resistant mutation for first- or second-generation EGFR-TKI. Journal of Thoracic Disease 9(3): 470-473, 2017

EGFR Gene Polymorphism Predicts Improved Outcome in Patients With EGFR Mutation-positive Non-small cell Lung Cancer Treated With Erlotinib. Clinical Lung Cancer 20(3): 161-166.E1, 2019

Phase II study of erlotinib for previously treated patients with EGFR wild-type non-small-cell lung cancer, following EGFR mutation status reevaluation with the Scorpion Amplified Refractory Mutation System. Molecular and Clinical Oncology 2(6): 991-996, 2014