title: BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients.
abstract: BACKGROUND
  This study aimed to determine whether the BRCA1 haplotype was associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients.
  
  
  METHODS
  We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour specimens from 135 advanced STS patients enrolled in published phase 2 trials or in a compassionate-use programme of trabectedin. Forty-four advanced STS patients treated with doxorubicin and 85 patients with localised STS served as controls. The 6-month nonprogression rate and overall survival (OS) were analysed according to BRCA1 haplotype using log-rank tests.
  
  
  RESULTS
  A favourable BRCA1 haplotype (presence of at least one AAAG allele) was significantly associated with an improved 6-month nonprogression rate. It was the only variable significantly associated with OS. No correlations were found between outcomes for patients with localised or advanced STS treated with doxorubicin.
  
  
  CONCLUSIONS
  The BRCA1 haplotype represents a potential DNA repair biomarker that can be used for the prediction of response to trabectedin in STS patients.
authors.affiliation: 1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Laroche-Clary
authors.affiliation: 1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
authors.forename: V
authors.initials: V
authors.lastname: Chaire
authors.affiliation: 1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
authors.forename: V
authors.initials: V
authors.lastname: Le Morvan
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Neuville
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Assistance Publique des Hôpitaux de Marseille, Hôpital la Timone, Marseille, France.
authors.forename: S
authors.initials: S
authors.lastname: Salas
authors.affiliation: Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Instituto Nazionale Tumori, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sanfilippo
authors.affiliation: 1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Pourquier
authors.affiliation: 1] INSERM U916 and University of Bordeaux, Bordeaux, France [2] Institut Bergonié, Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Italiano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D057176:Compassionate Use Trials / Q000706:statistics & numerical data; D004149:Dioxoles / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D000077606:Trabectedin; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin