title: Evaluation of BRCA1 mutations in an unselected patient population with triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and poor prognosis. While >50 % of patients with inherited BRCA1 mutations have TNBC, the prevalence of BRCA1 mutations in patients with TNBC remains unclear. Deciphering the relationship between BRCA1 and TNBC is critical to understanding the etiology of TNBC, leading to improved patient counseling and treatment. All female patients with TNBC enrolled in the Clinical Breast Care Project were identified. Genomic DNA was isolated from blood and the exonic regions of the BRCA1 gene were amplified and sequenced. Sequence data was analyzed and mutations identified using Sequencher 4.10.1. Of the 190 women with TNBC, genomic DNA was available for 182. Seventy percent of patients were considered high-risk for having a BRCA1 mutation based on the National Comprehensive Cancer Network criteria. Clinically relevant mutations were detected in 16 (9 %) patients ranging in age from 26 to 69 years at diagnosis. Six of these patients were diagnosed >50 years. The C61G mutation was found in three Caucasian women diagnosed >40 years, while six African-American women had mutations, including the 943ins10 West African founder mutation. Upon conclusion, causative BRCA1 mutations were detected in 9 % of TNBC patients, including patients without significant family histories and/or diagnosed at a later age. The mutation frequency in patients <60 years was 11.2-18.3 % in those patients with significant risk factors and 4.6 % in those without, while in patients >60 years, the mutation frequency was 3.5-7.7 % in patients with risk factors, 2.3 % in those without. Thus, evaluation of additional risk factors in both patients younger and older than 60 years should improve the identification of TNBC patients benefiting from genetic testing of BRCA1.
authors.affiliation: Windber Research Institute, 620 Seventh Street, Windber, PA 15963, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Rummel
authors.forename: Erika
authors.initials: E
authors.lastname: Varner
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ellsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C508053:ERBB2 protein, human