Abstract 813: Clinical significance of pathogenic variants in germline BRCA1/2 wild type patients at risk for hereditary breast cancer

Abstract Objectives: Approximately, 5-10% of breast cancer (BC) are related to inherited germline mutations. Homologous recombination repair (HRR) of DNA is the most important theory in hereditary cancer, in which BRCA1/2 are the most recognized and tested genes. Genetic testing for hereditary BC has changed significantly. Increasing evidence suggests parallel multigene testing of HRR gene. Methods: NGS-based germline multigene-panel testing of 105 HRR gene was performed on 159 high risk BC patients with at least one of the following risk factors: triple negative BC, early onset (≤45y), family history of BC and bilateral BC. Capture-base targeted sequencing was performed on white blood cells using a panel consisting of 105 genes related to homologous recombination repair of DNA. Results: Among the 159 patients of median age 40, All the patients had early stage infiltrating ductal carcinoma. 12 patients (7.55%) had pathogenic BRCA1/2 mutation. We investigated the prevalence of 21 pathogenic germline pathogenic mutations beyond BRCA1/2 from 21 patients spanning 13 HRR genes, resulting in a prevalence rate of 13.21% for pathogenic germline mutations in high risk germline BRCA1/2 WT BC patients. PALB2 is the most common gene with pathogenic mutation (n=5). In these 21 patients, 18 (85.71%) were diagnosed with BC before the age of 45, within 7 patients (33.33%) even younger than 35 years old. 7 of them (33.33%) had bilateral BC; one had triple negative BC (4.76%) and 5 patient (23.81%) had a family history of BC. Nearly half of the patients (n=9) presented at least 2 of the risk factors. Conclusions: Our study confirms the clinical significance of testing non-BRCA genes, and suggests multigene panel testing for patients at risk for hereditary BC as a routine in patients with those risk factors, especially young and bilateral BC patients even without family history of BC. Citation Format: Xiaying Kuang, Nan Shao, Ying Lin. Clinical significance of pathogenic variants in germline BRCA1/2 wild type patients at risk for hereditary breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 813.