Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant

PURPOSE: Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2 mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. MATERIALS AND METHODS: The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. RESULTS: The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. CONCLUSION: L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.