Pathologic predictors of BRCA1/ BRCA2 (B1/B2) mutations in African-American (AA) women with early-onset breast cancer (BC)

Abstract

10549 Background: African-American (AA) women more frequently have “triple negative” (ER-, PR-, HER2-) breast cancer (BC) and such BC are more frequently associated with B1 mutations; however, the correlation of triple negative BC in the AA population and B1/2 mutations is not known. We were interested in examining the prevalence of B1/2 mutations in a cohort of AA with early-onset breast as well as the associated pathologic characteristics. Methods: 85 unselected AA women diagnosed with 88 BC at or prior to age 40 were enrolled on study and underwent BRCA1/2 genetic testing by full sequencing at Myriad Genetics following informed consent. MLPA screening for large genomic rearrangements also was performed. Pathology reports were obtained and examined. Results: Of the 85 women, 16 (19%) had either a B1 (11) or B2 (5) deleterious mutation, which were associated with 19 BC. 19/85 (22%) women had a variant of unknown significance (VUS); 3 had B1 VUS, 15 had B2 VUS (including 2 with B1 mutations) and 1 had both B1 and B2 VUS. No mutations were detected with MLPA. Of the 14 BC in 11 B1 mutation carriers, 12 were ER- (86%), 13 were PR- (93%) and 3/12 were HER2+ (25%). Of the 5 BC in B2 carriers, 4 were ER- (80%), 1/4 HER2+ (25%). Receptor status was available in 77 of 88 cases (88%). Overall 41 of 77 (53%) cancers were ER-. 15 of 40 women (38%) with any ER- BC had either a B1 (11) or B2 (4) mutation. In contrast, of the 36 ER+ BC, 2 had a B1 and one had a B2 mutation (8%) (p=0.01). Both B1 carriers with ER+ BC also had a contralateral ER- BC. 18 of 65 (27%) cancers were known to be HER2+, of which 4 of 18 (22%) were associated with B1 or B2 mutations (p=NS). Median age of first BC in B1/B2 mutation carriers was 32 vs. 37 in non-carriers. Conclusions: In unselected AA women with early onset BC, B1/2 mutations were common and predominantly found in association with ER- BC. B2 VUS were detected frequently. HER2 overexpression did not predict against B1/2 mutations. No significant financial relationships to disclose.