title: Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing.
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.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Kansas Medical Center, 2330 Shawnee Mission Parkway, MS5003, Westwood, KS, 66205, USA, psharma2@kumc.edu.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sharma
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Klemp
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mahnken
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Geier
authors.forename: Qamar J
authors.initials: QJ
authors.lastname: Khan
authors.forename: Manana
authors.initials: M
authors.lastname: Elia
authors.forename: Carol S
authors.initials: CS
authors.lastname: Connor
authors.forename: Marilee K
authors.initials: MK
authors.lastname: McGinness
authors.forename: Joshua M W
authors.initials: JM
authors.lastname: Mammen
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Wagner
authors.forename: Claire
authors.initials: C
authors.lastname: Ward
authors.forename: Lori
authors.initials: L
authors.lastname: Ranallo
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Knight
authors.forename: Shane R
authors.initials: SR
authors.lastname: Stecklein
authors.forename: Roy A
authors.initials: RA
authors.lastname: Jensen
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics; D011446:Prospective Studies; D012042:Registries; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human