Abstract P1-10-01: Defining the spectrum of germline variants among African American patients with triple negative breast cancer
Authors: Pederson HJ , Heald B , Budd GT , Bernhisel R , Cummings S , Saam JR , Lancaster JM , Grobmyer SR , Eng C 
Published: May 2019

Abstract
Background: African American (AA) women are more likely to have breast cancer at a younger age and be diagnosed with triple negative breast cancer (TNBC), which is as yet unexplained. We examined results of multi-gene panel testing in AA women with TNBC tested at a large commercial laboratory to assess the utility of gene panels and findings in this group.
Methods: We assessed individuals who had clinical hereditary cancer testing with a multi-gene panel between September 2013 and May 2018. Women were included for analysis if they had a personal history of TNBC and self-identified as having any AA ancestry (n=3,268) or only Caucasian (CA) ancestry (n=8,953). Clinical data was collected from provider-completed test request forms. Comparisons were performed using descriptive statistics, t-tests (continuous variables), and chi-square tests (categorical variables) adjusting for multiple testing when necessary.
Results: In this cohort, AA women were significantly more likely than CA women to meet NCCN guidelines (97.5% vs. 96.6%, p=0.010) and significantly less likely to have an additional personal (16.2% vs. 21.8%, p&lt;0.001) or family (79.3% vs. 86.3%, p&lt;0.001) history of cancer. Overall, 11.5% of AA women were found to carry a pathogenic variant (PV) compared to 13.4% of CA women (p=0.004; Table 1). Compared to CA women, AA women with a PV were significantly younger at diagnosis (46.7 vs. 49.5 years of age; p&lt;0.001). The prevalence of PVs in BRCA1, CHEK2 and the Lynch syndrome genes was higher in CA women, whereas the prevalence of BRCA2 PVs was higher in AA women. While the prevalence of PVs in individual genes was not significantly different according to ancestry after adjusting for multiple comparisons, AA women were significantly less likely to have a PV in any breast cancer-related gene compared to CA women (p=0.048). AA women were significantly more likely to have a Variant of Uncertain Significance (VUS; 35.6% vs. 20.9%; p&lt;0.001) and to have &gt;1 VUS (8.6% vs. 2.6%, p&lt;0.001). Regardless of ancestry, patients diagnosed before age 40 were more likely to carry a PV (19.7% AA, 22.2% CA). However, the prevalence of PVs among patients diagnosed after age 60 was still striking (8.9% AA, 10.9% CA) and was similar to the PV prevalence among patients diagnosed between 40-60 (10.1% AA, 12.3% CA).
Conclusions: In the era of multi-gene panel testing, this large cohort of patients with TNBC supports the use of panel testing in AA women with TNBC regardless of age or additional personal/family history of cancer. While additional research to the rate and pathogenicity of VUS in AA women is needed, genetic counseling is necessary to explain the possibility and meaning of a VUS in this group.
Table 1.Distribution of PVs in BC-related genes according to ancestry AA WomenCA WomenGeneN (%)N (%)Any Breast Cancer-Related Gene347 (10.6)1104 (12.3)BRCA1132 (4.0)496 (5.5)BRCA297 (3.0)236 (2.6)ATM6 (0.2)25 (0.3)BARD119 (0.6)67 (0.7)BRIP120 (0.6)46 (0.5)CDH11 (&lt;0.1)1 (&lt;0.1)CHEK22 (0.1)33 (0.4)NBN2 (0.1)10 (0.1)PALB244 (1.3)138 (1.5)PTEN2 (0.1)4 (&lt;0.1)RAD51C20 (0.6)41 (0.5)STK1101 (&lt;0.1)TP532 (0.1)6 (0.1)Lynch Syndrome Genes10 (0.3)46 (0.5)Other Genes12 (0.4)24 (0.3)Multiple PVs6 (0.2)28 (0.3)Total (Any Gene)375 (11.5)1202 (13.4)
Citation Format: Pederson HJ, Heald B, Budd GT, Bernhisel R, Cummings S, Saam JR, Lancaster JM, Grobmyer SR, Eng C. Defining the spectrum of germline variants among African American patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-10-01.