Abstract P6-08-30: BRCA 1/2 tests and beyond, across a breast center population: 10 years analysis and review of mutations and variants of uncertain significance
Authors: Margossian Astrid L , Nicastro Ana I , Colica Maria V 
Published: March 2020

Introduction: In our “Breast Center Buenos Aires” population of 3854 patients, accessibility of BRCA1/2 testing started at 2009 and dramatically increased after Angelina Jolie’s double mastectomy press release in 2013. At the beginning, the only available test was BRCA1/2, and after 2016 a variety of commercial gene panels were available. Health insurances aleatory criteria of genetic testing approval and the lack of lab processing options in our country, made difficult accessibility for most of the patients. Objective: Analysis of BRCA1/2 and other cancer predisposition genetic panels testing across an Argentinean Breast Center population of 3854 patients from 2009 -2019. Analysis and reclassification of mutations and variants of uncertain significance (VUS) over the years, breast cancer subtypes and risk reduction strategies in mutation carriers. Results: 18 (16.07%) carriers with pathogenic mutations were found out of 112 tested patients, 13 (68,4%) in BRCA1, 4 (21.05%) in BRCA2 and 1 (0,89%) mutation in CHEK2 1100delC. From these 18 carriers, 14 (77.7%) had breast cancer, median age at diagnosis 40 years old. 8 (7.14%) VUS were reclassified as true VUS in June 2019, from 41 (36.6%) VUS reported originally. 4 in BRCA1/2, 1 in RAD51D, 1 in RAD51C, 1 in PALB2 and 1 in BRIP1 genes. One mutation was first founded in Argentina in 2009, now considered a “founder mutation" BRCA1 exon 11 c.2626_2627delAA. From 112 tested patients, 74 had personal history of breast cancer (66,07%), 4 LCIS (5,4%) 6 DCIS (8,1%) and 64 invasive carcinoma (86,5%): 37 luminal subtype (57,81%),10 Her2 + (15,62%) and 17 triple negative (26,56%). 7 of 17 patients with Triple negative tumors (41.17%) had a BRCA1 mutation. From 13 BRCA1 mutation carriers, 7 had triple negative breast cancer (53,84%). 2 patients had breast cancer diagnosis after genetic testing. 18 mutation carriers, 8(44,4%) had bilateral mastectomy and 5 (27.77%) bilateral oophorectomy. 3 (16.6%) carriers still continue in intensive imaging surveillance with mammography and/or MRI every 6 months. 1 of the carriers died at age 27 due a triple negative breast cancer and another died at age 60 because an ovarian cancer. Conclusion: Genetic testing has become a fundamental tool for multidisciplinary care of the breast cancer high-risk patient in the last ten years. The re- analysis and descrease of real VUSs over the years, based on new sequencing information from public databases, allowed a better management of these patients. We emphasize the importance of a 6 months follow up for reeavualate risks in VUS carriers.

Citation Format: Astrid L Margossian, Ana I Nicastro, Maria V Colica. BRCA 1/2 tests and beyond, across a breast center population: 10 years analysis and review of mutations and variants of uncertain significance [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-30.