Clinical Contrubution of Next-Generation Sequencing Multi- Gene Panel Testing for BRCA Negative High Risk Breast Cancer Patients

Abstract Background : Breast cancer is the most common malignancy in women and thought to be hereditary in 10% of patients. Recent next-generation sequencing (NGS) studies have increased the detection of pathogenic or likely pathogenic variants in genes other than BRCA1/2 in breast cancer patients. This study evaluated pathogenic variants, likely pathogenic variants, and variants of unknown significance (VUS) in 18 hereditary cancer susceptibility genes in BRCA1/2-negative breast cancer patients. Patients and Methods : This retrospective study included 188 high-risk BRCA1/2-negative breast cancer patients tested with a multi-gene cancer panel using NGS. Results : Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as pathogenic (P) or likely pathogenic (LP) in PALB2 (໿n = 6),໿ CHEK2 (n = 5), MUTYH (n = 4), ATM (n = 3), TP53 (n = 2), BRIP1 (n = 1) and MSH2 (n = 1). Three novel P/LP variants were identified. An additional 28 variants were classified as VUS and detected in 30 (15.9%) different patients. Conclusion : This is one of the largest study from Turkey to investigate the mutation spectrum in non-BRCA hereditary breast cancer susceptibility genes. A multi-gene panel test increased the likelihood of identifying a molecular diagnosis in BRCA 1/2-negative breast cancer patients at risk for a hereditary breast cancer syndrome. More studies are needed to enable the clinical interpretation of these P/LP variants in hereditary breast cancer patients. Next-generation sequencing (NGS) studies have increased the detection of pathogenic or likely pathogenic variants in genes other than BRCA1/2 in breast cancer patients. This study included 188 high-risk BRCA1/2-negative breast cancer patients tested with a multi-gene cancer panel using NGS. Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as pathogenic (P) or likely pathogenic (LP). A multi-gene panel increased the diagnosis success in BRCA1/2-negative high-risk breast cancer patients.