title: BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations.
abstract: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations.
  
  
  
  BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006).
  
  
  
  We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del.
  
  
  
  The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.|Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogotá, Colombia.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Cardona
authors.affiliation: Clinical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá, Colombia.|Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rojas
authors.affiliation: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Wills
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.|Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogotá, Colombia.
authors.forename: Hernán
authors.initials: H
authors.lastname: Carranza
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.|Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vargas
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.|Clinical and Traslational Research Department, Faculty of Medicine, Universidad el Bosque, Bogotá, Colombia.
authors.forename: Jorge
authors.initials: J
authors.lastname: Otero
authors.affiliation: Medical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica.
authors.forename: Luis
authors.initials: L
authors.lastname: Corrales-Rodriguez
authors.affiliation: Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Martín
authors.affiliation: Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Reguart
authors.affiliation: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Pilar
authors.initials: P
authors.lastname: Archila
authors.affiliation: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: July
authors.initials: J
authors.lastname: Rodríguez
authors.affiliation: Clinical Oncology Department, Hospital de Clínicas - UdeLAR, Montevideo, Uruguay.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cuello
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortíz
authors.affiliation: Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franco
authors.affiliation: Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital and Center for Oncological Research (CORE), Antwerp University, Edegem, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.lastname: on behalf of the CLICaP
mesh_terms: D044466:Asian People; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics*; D054316:Biomarkers, Pharmacological; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D017384:Sequence Deletion / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000072224:Bcl-2-Like Protein 11; D054316:Biomarkers, Pharmacological; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: BIM deletion; EGFR mutation; non-small-cell lung cancer; survival