Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

Eur J Hum Genet. 2015 May;23(5):588-95. doi: 10.1038/ejhg.2014.161. Epub 2014 Aug 20.

Abstract

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Testing*
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Netherlands / epidemiology
  • Referral and Consultation*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers, Tumor