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.

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

“…This is a much higher percentage than the 10-20% seen in other studies of patients with TNBC unselected for family history. 7,8,15 Considering the results from both our diagnostic and research cohorts, we wondered whether the high prevalence of mutation c.4183C4T in the Zillertal and LIV region is associated with an increased incidence of cancer. Detailed regional data from the Tyrolean Cancer Registry confirmed an increased risk for breast and ovarian cancer especially in the region of Zillertal with SIRs of 1.23 for breast cancer below the age of 50 and 2.13 years for ovarian cancer below the age of 65 years.…”

Association between Basal-Like Phenotype and BRCA1/2 Germline Mutations in Korean Breast Cancer Patients

“…Several studies have examined the prevalence of BRCA mutations in unselected tnbc patients [18][19][20][21] , and their authors have suggested that tnbc patients should be considered for BRCA1 and BRCA2 genetic testing based on the evidence of high BRCA mutation prevalence in unselected tnbc patients. Muendlein et al 18 assessed the prevalence of BRCA mutation in 100 unselected tnbc patients.…”

Síndrome de cáncer hereditario de mama y ovario: aplicación clínica

“…Los cánceres de mama asociados a la mutación del gen BRCA1 son con frecuencia negativos para la presencia de receptores de estrógeno, progesterona, y la sobreexpresión de HER-2/Neu (triple negativo) (30)(31)(32)(33). El 90 % de los tumores debidos a mutaciones en BRCA1 son triple negativos por inmunohistoquímica (19); además, en pacientes con tumores TN, la probabilidad de estar ligados a mutaciones BRCA1 es mayor que en las clasificadas como NO triple negativo, con un RR = 5,65 (IC 95 %: 4,15-7,69) (34); sin embargo, se desconoce la proporción exacta de tumores triple negativos que poseen mutaciones en BRCA1 (20).…”