Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)

Clin Transl Oncol. 2014 Mar;16(3):280-4. doi: 10.1007/s12094-013-1070-9. Epub 2013 Aug 27.

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.

Patients and 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.

Conclusion: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

MeSH terms

  • Adult
  • Age of Onset
  • Chromatography, High Pressure Liquid
  • DNA Mutational Analysis
  • Female
  • Genes, BRCA1*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism