Abstract P5-09-14: Prevalence and type of BRCA mutations in young breast cancer patients undergoing genetic cancer risk assessment in two developing countries: Analysis of two cohorts from Romania and Mexico

Abstract

Background: a previous study found significant clinicopathological differences between young Breast Cancer BrCA patients (pts) from Romania (Ro) and from Mexico (Mx). Here, we provide a molecular and clinical description of pts carrying BRCA mutations of both cohorts. Methods: in this retrospective study, we analyzed 2 cohorts of BRCA1/2 mutations carriers tested in COEI from Mx between 2014-2017 and IOCN from Ro between 2015 to 2016. Ro pts were selected according to NCCN criteria, while Mx pts were selected based on risk evaluation models. NGS analysis and MLPA for BRCA1&2 were performed in all pts. We compared demographic, clinicopathological and molecular data. Results: 65 pts, 21 (32.7%) from Mx and 44(67.7%) from Ro carried a BRCA mutation. 66.7% of Mx pts and 65.9% of Ro pts carried a BRCA1 mutation. We found clinical similarities: Mean age was 44.5y for Mx and 40.59y for Ro pts. IDC was the most frequent type of BrCa in both series (90.5 vs 90.9%). TNBC was seen in 13 Mx vs 27 Ro pts (61.9% vs 61.4%), HR positive was seen in 7 (33.3%) and 12 (27.3%) cases. Grading 3 was more frequently seen in Ro, while grading 2 was mainly noted in MX pts(p=<0.020). BRCA1/2 pathogenic mutations were different between the 2 cohorts and no BRCA 1/2 identical mutation was identified. 15 different mutations in 21 Mx pts, and 16 different mutations in 44 Ro pts were found. Mutations were different between 2 cohorts. Notably for the Ro cohort, 4 founder mutations (c.181T>G, c.3607C>T, c.5266dupC in BRCA1,and c.9928A>G[GPC1] in BRCA2) were found in 31/44 pts, while the Mx cohort, c.5123C>A and del 9-12del ex in BRCA1 were found in 6/21 mutations. Three Large rearrangements (LR) were exclusively seen in the Mx pts (5/21). Conclusions Both cohorts didn't share any mutation, but the clinical features are similar. BRCA1 del 9-12del is a Mexican founder mutation, we found it in 14% of Mx pts, LR have been described more frequently in Latin American Populations, we found it in 30% of the MX cohort, while for Ro cohort four recurrent mutations qualify as founder mutations. Citation Format: Campos-Gomez S, Antone N, Pacheco-Cuéllar G, Pop L, Campos Gomez K, Stoian A, Eniu R, Valdes-Andrade J, Dronca E, Matei R, Ligtenberg M, Ouchene H, Onisim A, Rotaru O, Eniu AE. Prevalence and type of BRCA mutations in young breast cancer patients undergoing genetic cancer risk assessment in two developing countries: Analysis of two cohorts from Romania and Mexico [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-14.