BRCA 1/2 mutations in high-grade serous ovarian cancer (HGS-OC) patients of three Latin American countries: Report of 412 cases.

Abstract

e14288 Background: Ovarian Cancer (OC) is the most common gynecologic cancer in women in the World and with elevated mortality. High Grade Serous Ovarian Cancer (HGS-OC) is a common histotype and closely related with the presence of BCRA abnormalities. This is to our knowledge the first report of a large series of patients with HGS-OC evaluated in Latin-American countries. The study aim was to present the data obtained from Perú, Costa Rica and Panamá from January 2016 to December 2018. Methods: A cross-sectional evaluation was performed in patients diagnosed between 2016 and 2018 with HGS-OC in three countries in Latin America. The patients were selected from Cancer National Reference Centers in Perú, Panamá and Costa Rica. Germline BRCA 1 / 2 mutations were evaluated through Next Generation Sequencing (NGS) in blood samples. Results: During the period 412 HGS-OC were studied. The mean age at diagnosis was 56.55(SD:12.21) years for all the evaluated patients and 55.42(SD:8.60) years in the mutated cases. Pathogenic HGS-OC mutations in germline BRCA 1 / 2 were diagnosed in 72 cases. Germline BRCA 2 mutations were the most frequent abnormality detected in Panama and in Costa Rica with 70.0 %(7/10) and 77.8%(14/18), respectively. However in Perú, germline mutations in BRCA 1 represents the majority of the mutations with 79.3%(35/44). Variants of uncertain significance (VUS) were detected in 3.64 %(15/412). Positive family history for breast or ovarian cancer were detected in 13.8% of patients with pathogenic mutations(10/72). Specific mutation distribution evidenced in Perú that 6 of 44(13.6%) mutated patients had the mutation in BRCA 1 c.2105dupT; 6 patients of 18(33.3%) had the mutation in BRCA 2 c.5303_5304delTT in Costa Rica and 2 cases had the mutation in BRCA1 c.5186C > A in Panama. The rest of mutations were less common. Conclusions: The frequency of Germline mutations BRCA 1 and BRCA 2 in patients with HSG-OC is similar to the reported in developed nations. However, the different mutation profile between the studied countries could be explained by the Latin-American genetic diversity. Most of the mutations we report were not described in previous studies evaluating breast cancer susceptibility.