Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: Implications for hereditary breast and/or ovarian cancer syndrome testing

Priyanka Sharma, Jennifer R. Klemp, Bruce F. Kimler, Jonathan D. Mahnken, Larry J. Geier, Qamar J. Khan, Manana Elia, Carol S. Connor, Marilee K. McGinness, Joshua M.W. Mammen, Jamie L. Wagner, Claire Ward, Lori Ranallo, Catherine J. Knight, Shane R. Stecklein, Roy A. Jensen, Carol J. Fabian, Andrew K. Godwin

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged &60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I-IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African-American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (&50 years), 11.4 % (51-60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p =.0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC.

Original languageEnglish (US)
Pages (from-to)707-714
Number of pages8
JournalBreast Cancer Research and Treatment
Volume145
Issue number3
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Genetic testing guidelines
  • Germline BRCA mutation
  • NCCN guidelines
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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