Abstract P4-06-04: Germline alterations in African-American versus Caucasian patients with triple-negative breast cancer in the era of multi-gene panel testing

Abstract

Abstract Background. Triple negative breast cancer (TNBC) has been associated with a relatively high rate of germline BRCA1/2 deleterious mutations (11-20%). With use of panel testing, additional predisposition genes are being identified. Among Caucasian (CC) patients (pts), pathogenic germline variants in BRCA1/2 are mainly associated with TNBC. However, these may not fully explain the higher incidence of TNBC among African Americans (AA). Additionally, partly due to under-testing among AA, the distribution of predisposition genes for AA TNBC pts is unknown, and a greater proportion of germline alterations may be classified as a variant of uncertain significance (VUS). We hypothesized that additional clinically significant germline mutations in genes, other than in BRCA1/2, may explain the increased incidence of TNBC among AA, which may be better elucidated by panel testing. Methods. A retrospective chart review was completed of all self-identified CC and AA TNBC pts who presented to two institutions from 10/2013 to 12/2016. A total of 596 pts were analyzed. 434 (73%) were CC and 162 (27%) were AA. Clinicopathologic features including histologic subtype, age, gender, bilateral disease and stage were examined. Patients were assessed for meeting the National Comprehensive Cancer Network (NCCN) criteria for genetic testing in TNBC, type of testing performed, and the results. The distribution of mutations in higher penetrance genes (BRCA1, BRCA2, and PALB2), pathogenic variants in other genes, and VUS in AA vs. CC were analyzed. Significance was determined using a two-tailed Fisher exact test with significance of p<0.05. Results. 306/434 (71%) CC and 98/162 (60%) AA TNBC pts met criteria for genetic testing (p=0.023). For those who met NCCN criteria for testing, 216/306 (71%) CC and 66/98 (67%) AA TNBC pts underwent testing (p=0.61). For all pts, the average age of first diagnosis was 59.5 (SD 14) for CC vs. 62.4 (SD 12.9) for AA pts. For pts who underwent testing, regardless of meeting NCCN criteria, 18% (40/221) of CC vs.12% (8/68) of AA patients had a mutation in a higher penetrance gene (p=0.27), 1% (3/221) of CC vs. 3% (2/68) of AA had a mutation in other genes (BRIP1, Lynch genes; p=0.34), and 16% (36/221) of CC vs. 18% (12/68) of AA had a VUS (p=0.982). Of VUS, 42% (5/12) in AA vs. 19% (7/36) in CC were in higher penetrance breast cancer genes (p=0.14). Conclusion. More CC than AA TNBC pts met criteria for genetic testing. This difference may in part be explained by the later age at diagnosis for AA given that age is a major factor in determining genetic testing. Broadening eligibility for testing in AA may help to identify more patients with an underlying genetic predisposition to TNBC. No difference was seen in the frequency of higher penetrance genes, other genes, and VUS between AA and CC pts. However, important non-BRCA genes were identified with panel testing in both AA and CC pts. In addition to broadening testing criteria for existing multi-gene panels, further genetic analysis may be necessary to explain the predisposition to TNBC in AA pts. To our knowledge, this is the first report of evaluation of predisposition genes among AA TNBC pts using germline panel testing. Citation Format: Nizialek EA, Gopalakrishnan D, Yanda C, Abbas H, Kline M, Stephens M, Grobmyer SR, Eng C, Mitchell A, Pederson H, Vinayak S. Germline alterations in African-American versus Caucasian patients with triple-negative breast cancer in the era of multi-gene panel testing [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-04.