Genetic risk assessment and prevention: the role of genetic testing panels in breast cancer

Expert Rev Anticancer Ther. 2015;15(11):1315-26. doi: 10.1586/14737140.2015.1090879. Epub 2015 Nov 2.

Abstract

Multigene panel tests are being increasingly used for the genetic assessment of women with an apparent predisposition to breast cancer. Here, we review all studies reporting results from individuals who have undergone multigene panel testing for hereditary breast cancer. Across all gene panel studies, the prevalence of pathogenic mutations was highest in BRCA1 (5.3%) and BRCA2 (3.6%) and was lowest in PTEN (0.1%), CDH1 (0.1%) and STK11 (0.01%). After BRCA1/2, the prevalence of pathogenic mutations was highest in CHEK2 (1.3%), PALB2 (0.9%) and ATM (0.8%). The prevalence of variants of unknown significance was highest in ATM (9.6%). Based on the prevalence and penetrance of pathogenic mutations and the prevalence of variants of unknown significance, it is our interpretation that BRCA1, BRCA2, PALB2 and CHEK2 are the best candidates for inclusion in a clinical multigene breast cancer panel.

Keywords: breast cancer; gene panel; genetic testing; next-generation sequencing; precision medicine.

Publication types

  • Review

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Checkpoint Kinase 2 / genetics
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods*
  • Humans
  • Mutation
  • Nuclear Proteins / genetics
  • Risk Assessment / methods
  • Tumor Suppressor Proteins / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins
  • Checkpoint Kinase 2
  • CHEK2 protein, human