Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients

Abstract

Purpose: Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant. Materials and Methods: This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants were reviewed. Results: A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All seven cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected. Conclusion: We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.