A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes

Cancer. 2017 May 15;123(10):1721-1730. doi: 10.1002/cncr.30498. Epub 2017 Jan 13.


Background: As panel testing becomes more common in clinical practice, it is important to understand the prevalence and trends associated with the pathogenic variants (PVs) identified. This is especially true for genetically heterogeneous cancers, such as breast cancer (BC), in which PVs in different genes may be associated with various risks and cancer subtypes. The authors evaluated the outcomes of genetic testing among women who had a personal history of BC.

Methods: A total of 35,409 women with a single diagnosis of BC who underwent clinical genetic testing with a 25-gene panel were included in the current analysis. Women with multiple BCs and men with BC were excluded. The frequency and distribution of PVs were assessed for the overall cohort, among women with triple-negative BC (TNBC) (n = 4797), and by age at diagnosis.

Results: PVs were identified in 9.3% of women tested; 51.5% of PVs were identified in genes other than breast cancer 1 (BRCA1) and BRCA2, including checkpoint kinase 2 (CHEK2) (11.7%), ataxia telangiectasia mutated (ATM; ATM serine/threonine kinase) (9.7%), and partner and localizer of BRCA2 (PALB2) (9.3%). The prevalence of PVs in BRCA1, PALB2, BRCA1-associated RING domain 1 (BARD1), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and RAD51 paralog C (RAD51C) was statistically higher among women with TNBC. The PV rate was higher among women aged <40 years, lower among women aged >59 years, and relatively constant (8.5%-9.0%) among women who were diagnosed between ages 40 and 59 years.

Conclusions: These results demonstrate that panel testing increased the number of women identified as carrying a PV in this cohort compared with BRCA testing alone. Furthermore, the proportion of women identified who carried a PV in this cohort did not decrease between ages 40 and 59 years. Cancer 2017;123:1721-1730. © 2017 American Cancer Society.

Keywords: BRCA2; breast cancer type 1 (BRCA1); hereditary breast and ovarian cancer; panel testing; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2 / genetics
  • DNA-Binding Proteins / genetics
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Testing
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics*
  • Humans
  • Lynch Syndrome II / genetics*
  • Middle Aged
  • Neoplastic Syndromes, Hereditary / genetics
  • Nuclear Proteins / genetics
  • RNA Helicases / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Young Adult


  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • PALB2 protein, human
  • RAD51C protein, human
  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human
  • BRIP1 protein, human
  • RNA Helicases