Abstract P5-10-04: Spectrum of hereditary breast and ovarian cancer gene variants in an African American cohort

Abstract

Abstract Background: Few reports describe the spectrum of mutations in breast and ovarian cancer predisposition genes found specifically in African Americans. Methods: 560 women who self-identified as African American (AA) from the University of Pennsylvania and Wayne State University were included in this IRB-approved, case-control study. Cases (n=218 with a personal history of breast and/or ovarian cancer) and controls (n=342 without breast or ovarian cancer) underwent germline genetic testing using the Color Genomics 19-gene breast and ovarian cancer risk panel. The subset of AA patients diagnosed with breast cancer ≤40 (n=185) was compared to an institutional cohort of white patients with breast cancer diagnosed ≤40 (n=189). Results: Of 218 AA cases, 70 had pathogenic or likely pathogenic (P/LP) mutations (BRCA1: n=36; BRCA2: n=24; TP53: n=3; RAD51D: n=2; ATM: n=2; CHEK2: n=2 and MSH6: n=1). Forty-two of 218 patients (19%) had at least one variant of uncertain significance (VUS). Of 342 AA controls, 5 women had P mutations in 5 distinct genes: BRCA2, ATM, BRIP1, PALB2 and PMS2. 55 control patients (16%) had at least one VUS. Many of the 75 P/LP mutations (cases, 70 mutations; controls, 5 mutations) in the full AA cohort were unique variants. In the 135 patients who had BRCA1/BRCA2 sequencing prior to testing under this protocol, the Color Genomics platform identified all 56 pathogenic mutations. Among AA patients diagnosed with breast cancer ≤40 (n=185), the incidence of TP53 and ATM pathogenic mutations was similar to the white, early-onset breast cancer cohort (n=189): TP53, 1% in both cohorts; ATM = 1% in AA patients and 2% in whites. However, no patients in the AA, early-onset cohort had germline CHEK2 mutations, compared to 4% of white, early-onset breast cancer patients (p=0.007). Conclusions: Taken together, the results of this study demonstrate the importance of considering germline mutation testing in the AA population. Examination of mutations and disease phenotypes within the AA population may facilitate understanding of the clinical risk associated with variants of uncertain significance. Further comparative data between the AA and white cohorts will be presented. Citation Format: Shah PD, Digiovanni L, Maxwell KN, Bradbury AR, Van Den Akker J, Kim S, Gil E, Simon MS, Nathanson KL, Domchek SM. Spectrum of hereditary breast and ovarian cancer gene variants in an African American cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-10-04.