Cited by 307Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Diagnosis and Treatment

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Pretreatment EGFR T790M Mutation and BRCA1 mRNA Expression in Erlotinib-Treated Advanced Non–Small-Cell Lung Cancer Patients with EGFR Mutations

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Rosell, Rafael, Molina, Miguel Angel, Costa, Carlota, Simonetti, Sara, Gimenez-Capitan, Ana, Bertran-Alamillo, Jordi, Mayo, Clara, Moran, Teresa, Mendez, Pedro, Cardenal, Felipe, Isla, Dolores, Provencio, Mariano, Cobo, Manuel, Insa, Amelia, Garcia-Campelo, Rosario, Reguart, Noemi, Majem, Margarita, Viteri, Santiago, Carcereny, Enric, Porta, Ruth, Massuti, Bartomeu, Queralt, Cristina, de Aguirre, Itziar, Sanchez, Jose Miguel, Sanchez-Ronco, Maria, Mate, Jose Luis, Ariza, Aurelio, Benlloch, Susana, Sanchez, Jose Javier, Bivona, Trever G, Sawyers, Charles L, Taron, Miquel·2011·Clinical Cancer Research

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

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Abstract

PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

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Outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) according to the presence of the EGFR T790M mutation and BRCA1 mRNA expression levels in pretreatment biopsies.
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Authors: Rosell, R., Molina, M. A., Costa, C., Simonetti, S., Gimenez-Capitan, A., Bertran-Alamillo, J., Mayo, C., Moran, T., Mendez, P., Cardenal, F., Isla, D., Provencio, M., Cobo, M., Insa, A., Garcia-Campelo, R., Reguart, N., Majem, M., Viteri, S., Carcereny, E., Porta, R., Massuti, B., Queralt, C., de Aguirre, I., Sanchez, J. M., Sanchez-Ronco, M., Mate, J. L., Ariza, A., Benlloch, S., Sanchez, J. J., Bivona, T. G., Sawyers, C. L., & Taron, M.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Authors' Affiliations: 1Catalan Institute of Oncology, Hospital Germans Trias i Pujol; 2Hospital Germans Trias i Pujol, Badalona, Spain; 3USP Dexeus University Institute, Pangaea Biotech; 4Hospital Clinic; and 5Hospital Sant Pau, Barcelona, Spain; 6Catalan Institute of Oncology, Hospital Duran i Reynals, Bellvitge, Spain; 7Hospital Lozano Blesa, Zaragoza, Spain; 8Hospital Puerta de Hierro; 9MD Anderson; and 10Autonomous University of Madrid, Madrid, Spain; 11Hospital Carlos Haya, Malaga, Spain; 12Hospital Clinico Universitario, Valencia, Spain; 13Hospital Juan Canalejo, La Coruña, Spain; 14Catalan Institute of Oncology, Hospital Josep Trueta, Girona, Spain; 15Hospital General, Alicante, Spain; 16University of Alcala de Henares, Alcala de Henares, Spain; 17Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York; and 18Howard Hughes Medical Institute, Chevy Chase, Maryland
Corresponding author: Rosell, Rafael
ORCID: Rosell, Rafael
Simonetti, Sara
Isla, Dolores
Provencio, Mariano
Cobo, Manuel
Insa, Amelia
Majem, Margarita
Viteri, Santiago
Carcereny, Enric
Queralt, Cristina
Bivona, Trever G
Sawyers, Charles L
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2011-03-01
Volume: 17
Issue: 5
Pages: 1160-1168
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-10-2158
OpenAlex: W2156560090
Cited by: 304
References: 48
Citations by year: 2026: 2 · 2025: 3 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 20 · 2018: 20 · 2017: 34 · 2016: 31 · 2015: 33 · 2014: 37 · 2013: 47 · 2012: 23
FWCI: 33.19
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: T790M mutation, BRCA1 mRNA expression, erlotinib, advanced non-small cell lung cancer, EGFR mutation, exon 19 deletion, L858R mutation, progression-free survival, DNA repair pathways, predictive biomarkers, personalized treatment
MeSH terms: Erlotinib Hydrochloride, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, DNA Repair, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Quinazolines, RNA, Messenger, Biomarkers, Tumor, Gene Expression, Treatment Outcome, Disease-Free Survival, Genes, erbB-1, BRCA1 Protein, Genes, BRCA1, Receptor Protein-Tyrosine Kinases, Protein Kinase Inhibitors, ErbB Receptors

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Pretreatment EGFR T790M Mutation and BRCA1 mRNA Expression in Erlotinib-Treated Advanced Non–Small-Cell Lung Cancer Patients with EGFR Mutations

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