title: Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC).
abstract: BACKGROUND
  BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported.
  
  
  METHODS
  From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors.
  
  
  RESULTS
  Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype.
  
  
  CONCLUSIONS
  Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.
authors: Servicio de Oncología Médica, Hospital Clínico Lozano Blesa, San Juan bosco 15, 50009, Zaragoza, Spain, andresraquel@hotmail.com.
authors: R
authors: R
authors: Andrés
authors: I
authors: I
authors: Pajares
authors: J
authors: J
authors: Balmaña
authors: G
authors: G
authors: Llort
authors: T
authors: T
authors: Ramón Y Cajal
authors: I
authors: I
authors: Chirivella
authors: E
authors: E
authors: Aguirre
authors: L
authors: L
authors: Robles
authors: E
authors: E
authors: Lastra
authors: P
authors: P
authors: Pérez-Segura
authors: N
authors: N
authors: Bosch
authors: C
authors: C
authors: Yagüe
authors: E
authors: E
authors: Lerma
authors: J
authors: J
authors: Godino
authors: M D
authors: MD
authors: Miramar
authors: M
authors: M
authors: Moros
authors: P
authors: P
authors: Astier
authors: B
authors: B
authors: Saez
authors: M J
authors: MJ
authors: Vidal
authors: A
authors: A
authors: Arcusa
authors: S
authors: S
authors: Ramón y Cajal
authors: M T
authors: MT
authors: Calvo
authors: A
authors: A
authors: Tres
mesh_terms: D000328:Adult; D017668:Age of Onset; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D012189:Retrospective Studies; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism
references: Clin Cancer Res. 2001 Jun;7(6):1739-42
references: 11410514
references: J Clin Oncol. 2010 Sep 20;28(27):4214-20
references: 20733129
references: BMC Cancer. 2009 Mar 19;9:86
references: 19298662
references: Am J Surg Pathol. 2009 Jul;33(7):1093-7
references: 19390427
references: Breast Cancer Res Treat. 2005 Mar;90(1):5-14
references: 15770521
references: Int J Cancer. 1999 Jun 21;84(3):263-7
references: 10371344
references: Nat Genet. 1994 Dec;8(4):392-8
references: 7894492
references: J Clin Oncol. 2002 May 1;20(9):2310-8
references: 11981002
references: JAMA. 2007 Jun 20;297(23):2587-95
references: 17579227
references: J Natl Cancer Inst. 2003 Oct 1;95(19):1482-5
references: 14519755
references: Breast Cancer Res. 2005;7(1):R93-100
references: 15642173
references: Cancer Res. 2000 Mar 1;60(5):1206-10
references: 10728676
references: Breast Cancer Res. 2005;7(4):R465-9
references: 15987451
references: Clin Cancer Res. 2005 Jul 15;11(14):5175-80
references: 16033833
references: Breast Cancer Res. 2010;12(3):R28
references: 20482762
references: J Clin Oncol. 2006 Feb 1;24(4):707-15
references: 16446345
references: Clin Cancer Res. 2001 Jul;7(7):1937-45
references: 11448907
references: Cancer. 2012 Jun 1;118(11):2787-95
references: 22614657
references: Am J Hum Genet. 1998 Mar;62(3):676-89
references: 9497246
references: Clin Cancer Res. 2004 Mar 15;10(6):2029-34
references: 15041722
references: Br J Cancer. 2012 Mar 13;106(6):1234-8
references: 22333603
references: Am J Surg Pathol. 2006 Nov;30(11):1357-66
references: 17063074