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Clinical Contribution of Next-Generation Sequencing Multigene Panel Testing for BRCA Negative High-Risk Patients With Breast Cancer

Published:April 12, 2021DOI:https://doi.org/10.1016/j.clbc.2021.04.002

      Abstract

      Background

      Breast cancer is the most common malignancy in women and thought to be hereditary in 10% of patients. Recent next-generation sequencing studies have increased the detection of pathogenic or likely pathogenic (P/LP) variants in genes other than BRCA1/2 in patients with breast cancer. This study evaluated pathogenic variants, likely pathogenic variants, and variants of unknown significance in 18 hereditary cancer susceptibility genes in patients with BRCA1/2-negative breast cancer.

      Patients and Methods

      This retrospective study included 188 high-risk BRCA1/2-negative patients with breast cancer tested with a multigene cancer panel using next-generation sequencing.

      Results

      Among 188 proband cases, 18 variants in 21 patients (11.1%) were classified as P/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 variants of unknown significance and detected in 30 different patients (15.9%).

      Conclusion

      This is one of the largest study from Turkey to investigate the mutation spectrum in non-BRCA hereditary breast cancer susceptibility genes. A multigene panel test increased the likelihood of identifying a molecular diagnosis in patients with BRCA 1/2-negative breast cancer at risk for a hereditary breast cancer syndrome. More studies are needed to enable the clinical interpretation of these P/LP variants in hereditary patients with breast cancer.

      Keywords

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