A multi-institutional study on the association between BRCA1/BRCA2 mutational status and triple-negative breast cancer in familial breast cancer patients

Breast Cancer Res Treat. 2014 Jul;146(1):63-9. doi: 10.1007/s10549-014-3006-7. Epub 2014 Jun 4.

Abstract

Triple-negative breast cancer (TNBC) accounts for 12-24 % of all breast cancers. Here, we studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements (LGRs) as well as sequence variants, and investigated the association between BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative patients were screened for LGRs. In this study, the prevalence of BRCA1/2 mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in 35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers. Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC prevalence in BRCA1 mutation carriers was significantly lower when there was a family history of ovarian cancer. Our multinomial logistic regression model demonstrated that no single factor was sufficient, and at least two factors, such as a patient with family history of both breast cancer and ovarian cancer or a patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype, are necessary to indicate BRCA1/2 genetic testing in this population. Our results suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in this population, but additional risk factors should also be evaluated to ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics
  • Prevalence
  • Prognosis
  • Republic of Korea / epidemiology
  • Risk Factors
  • Triple Negative Breast Neoplasms / epidemiology
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • Young Adult

Supplementary concepts

  • Breast Cancer, Familial