Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer.

Purpose: To clarify the status of multigene panel testing for suspected hereditary breast cancer in our institute, and disclose the characteristics of the variants detected.

Methods: This was a retrospective study of individuals who underwent next-generation sequencing-based multigene panel testing at our institute to investigate hereditary genetic variants for suspected hereditary breast cancer.

Results: We identified 36 women who underwent multigene panel testing: 8 (22.2%) had a pathogenic variant, with or without other variants of uncertain significance (VUSs); 15 (41.7%) had VUSs only; and 13 (36.1%) had negative genetic test results. Of the eight pathogenic variants, five were BRCA2 variants and one each were BRCA1, MLH1, and RINT1 variants. The VUSs included BRCA1 and BRCA2, as well as other breast cancer-associated genes, such as ATM, CDH1, CHEK2, and PALB2. Referring to the latest ClinVar database, one of the variants identified as a VUS at diagnosis was re-determined as likely pathogenic, and three of the variants identified as VUSs at diagnosis were re-determined as benign.

Conclusion: VUSs are frequently identified during testing and it is important to monitor these individuals because VUS evaluations can change over time.