Abstract P4-12-06: Results of next-generation sequencing panels in a large community-based hereditary cancer risk program

Abstract

Abstract Background: Next-generation sequencing (NGS) allows for broader germline genetic testing for hereditary cancers. Since the Supreme Court decision of AMP v. Myriad on June 13, 2013, hereditary cancer multi-gene panels can now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions have been raised about the clinical utility and implications of extended panels for medical management given the inclusion of unknown to moderate penetrant genes. Methods: We reviewed all patients who underwent multi-gene panel testing from July 1, 2013 through May 23, 2014. The indications for testing included personal and/or family history of breast or ovarian cancer. The panels were ordered in a single genetic counseling clinic within a large community-based cancer center. Results: A total of 136 patients underwent panel testing via a single commercial laboratory. We identified 12 (8.8%) patients who were positive for a pathogenic or likely pathogenic mutation in a cancer susceptibility gene; 4 had prior negative BRCA1 and BRCA2 sequencing and deletion/duplication testing. These positive results included 4 BRCA2 mutations, 2 TP53 mutations, 1 CDH1 mutation, 2 ATM mutations, and 1 patient each with a CHEK2, NBN, or PALB2 mutation. Of the patients found to have a positive test result, 100% met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer (HBOC) genetic testing. The CDH1 mutation carrier did not meet NCCN guidelines for hereditary diffuse gastric cancer testing and only one of the TP53 mutation carriers met NCCN guidelines for Li-Fraumeni syndrome. Within our cohort (136), 21 (15.4%) patients had a total of 25 variants of uncertain significance (VUS) and 103 (75.7%) patients had negative test results. Conclusion: Testing through NGS panels identified 7/12 (58%) patients with a mutation which led to changes in current medical management and 3/7 (43%) had a mutation in a gene other than BRCA1 or BRCA2. Our findings suggest that there is clinical utility of NGS panels for use in this patient population despite the inclusion of unknown to moderate penetrant genes and a higher rate of VUS than single gene testing. Citation Format: J L Blum, C A Garby, A E Simmons, S A Walker, L E Panos. Results of next-generation sequencing panels in a large community-based hereditary cancer risk program [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-06.