Abstract PS8-16: Differences in the benefit of multi-gene panel (MGP) genetic testing between African American and white women with invasive breast cancer
Authors: Whitaker Kristen , Ventriglia Nicole , Devarajan Karthik , Obeid Elias 
Published: February 2021

Background: Up to 10% of breast cancers are hereditary. Pathogenic variants (PV) in the BRCA1/2 genes are responsible for two thirds of hereditary breast cancer (BC). Additional non-BRCA genes (ATM, CHEK2, PALB2, etc.) have been identified as predisposing for BC. While genetic testing(GT) for hereditary BC traditionally involved testing mostly for mutations in the BRCA1/2 genes, next generation sequencing has enabled multiple BC genes to be simultaneously tested at a cost often lower than testing for BRCA1/2 alone. Consequently, MGP testing has been rapidly replacing BRCA1/2 only testing. Studies have demonstrated that MGP testing doubles the detection of PV. Because prior studies examining MGP findings have been mostly conducted in predominantly white populations, it is unknown if the use of MGP testing in African-American (AA) patients also results in increased detection of non-BRCA mutations and whether there are significant differences in the prevalence of PV between AA and white women with invasive BC. In this study, we sought to compare the rate and spectrum of PV between AA and White women with invasive BC undergoing MGP testing. Methods: In this retrospective study, we assessed the prevalence of PV and spectrum of mutations among a cohort of 680 racially diverse women diagnosed with invasive BC who underwent GT with a MGP between 2014 and 2019 at a single cancer center. This analysis included participants who had a documented diagnosis of invasive BC and completed MGP testing. Fisher’s exact tests were used to analyze differences between racial groups. Subjects previously signed informed consent to participate in research. Results: 680 women with invasive BC were included in the study. The study population was 79.4% non-Hispanic white, 10.6% AA, and 10% other. PV were identified in 13.4 % of the overall population. The prevalence of PV was 15.5% (84/540) in AA compared to 8.3% (6/72) in white women, but this difference was not statistically significant (p=0.14). In white women, the prevalence of PV was 5.9% (32/540) in BRCA1/BRCA2 and 9.6% (52/540) in non-BRCA genes. MGP testing allowed for the detection of 52 non-BRCA PV, including BC genes (CHEK2-17, ATM-7, PALB2-4, CDH1-2, BARD1-1, TP53-1, RAD50-1) and non-BC genes (MUTYH-8, NTHL1-2, BRIP1-2, PMS2-2, RAD51C-1, RAD51D-1, MSH6-1, FH-1, MITF-1). In AA patients, the prevalence of PV was 6.9% in BRCA1/2 and 1.4% in non-BRCA genes. MGP testing in AA women with invasive BC detected only one non-BRCA mutation in the gene MUTYH. VUS rates were higher in AA, 29.2% compared to whites, 19.3% with a trend towards a statistically significant difference (p=0.07). Conclusions: While MGP testing more than doubled the detection rate of PV in white patients with BC by detecting various non-BRCA PV, for AA patients the use of MGP testing did not result in many additional non-BRCA PV being identified in this analysis. However, MGP testing did result in a high VUS rate, 19.3%, without the added value of detecting additional PV that could be helpful to the patient and their family members by expanding opportunities for cancer prevention and early detection. We acknowledge that in this study sample of 10.6% AA women, this is an under-representation. Large population-specific studies should be done to confirm those findings. Given the known psychological harms to the patient and their family members in response to the uncertainty of VUS findings as well as the possible mismanagement of VUS results, well-designed studies should investigate the selection of who to consider for MGP testing rather than BRCA1/2 testing for hereditary BC to ensure that the benefits of MGP testing over BRCA1/2 only testing outweigh the risks associated with panel testing.

Citation Format: Kristen Whitaker, Nicole Ventriglia, Karthik Devarajan, Elias Obeid. Differences in the benefit of multi-gene panel (MGP) genetic testing between African American and white women with invasive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-16.