Abstract P2-09-06: Multi-gene panel testing for hereditary cancer risk

Abstract

Abstract Background: Multi-gene panels are widely available for assessing hereditary cancer risk in high risk individuals. Due to the use of these panels, many genetic mutations other than BRCA 1 or 2 can be detected which can potentially affect management. This study presents the results of multi-gene panel testing performed at Beaumont Health System. Methods:All patients who underwent multi-gene panel testing at Beaumont Health System between November 1, 2012 and January 15, 2015 were included in this study. This cohort consisted of patients who met criteria for genetic testing due to personal or family history. All patients received comprehensive pre and post-test genetic counseling. The panels ranged from 5 to 43 genes associated with risk for breast and other cancers. Results: 653 multi-gene panel tests were performed. The majority of these consisted of either a 5 gene high risk breast panel (25%), an 18 gene moderate to high risk breast panel (21%), or a 9 gene high risk breast and gynecologic panel (17%). 184 variants of undetermined significance (VUS) were identified with a pooled VUS rate of 28%. Among the commonly used panels, there was a positive correlation between VUS rate and the number of genes included in the panel (r = 0.86, p = 0.01, Range 6% to 70%). A pathogenic mutation was identified in one or more genes in 65 (10%) panels for a total of 67 mutations. Of these, 17 mutations were in BRCA1 or BRCA2 gene. Fifty non-BRCA deleterious mutations were identified with the following frequencies: CHEK2(12), MUTYH(7 monoallelic, 1 biallelic), TP53(4), PTEN(4), ATM(4), MSH6(3), PALB2(3), MSH2(2), CDH1(2), APC(2), NF1(2), BARD1(2), MLH1(1) and PMS2(1). Of these non-BRCA mutations, 41(82%) had a significant impact on management. Conclusions: Our study demonstrates that multi-gene panel testing identifies several genes that can impact management and would likely not have been discovered by pedigree analysis alone. However, this added detection is associated with a higher VUS rate, especially using larger panels. Further research is needed to better define the role of multi-gene panel testing in high risk patients, with a focus on choosing appropriate genes, understanding the magnitude of cancer risk and delineating impact on management. Citation Format: Yadav S, Ladkany R, Fulbright J, Dreyfuss H, Reeves A, Campian S, Thomas V, Zakalik D. Multi-gene panel testing for hereditary cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-06.