Mutational Analysis of BRCA1 and BRCA2 Genes in Breast Cancer Patients from Eastern Sicily

Stefania Stella,1,2 Silvia Rita Vitale,1,2 Federica Martorana,1,2 Michele Massimino,1,2 Giuliana Pavone,3 Katia Lanzafame,3 Sebastiano Bianca,4 Chiara Barone,5 Cristina Gorgone,6 Marco Fichera,6,7 Livia Manzella1,2 1Department of Clinical and Experimental Medicine, University of Catania, Catania, 95123, Italy; 2Center of Experimental Oncology and Hematology, A.O.U. Policlinico “G. Rodolico - San Marco”, Catania, 95123, Italy; 3Medical Oncology, A.O.U. Policlinico “G. Rodolico - San Marco”, Catania, 95123, Italy; 4Medical Genetics, ARNAS Garibaldi, Catania, 95123, Italy; 5Medical Genetics, ASP, Siracusa, 96100, Italy; 6Department of Biomedical and Biotechnological Sciences, Medical Genetics, University of Catania, Catania, 95123, Italy; 7Oasi Research Institute-IRCCS, Troina, 94018, ItalyCorrespondence: Stefania Stella, Tel +39 095 378 1946, Email stefania.stella@unict.it; stefania.stel@gmail.comPurpose: Germline mutations of BRCA1 and BRCA2 are associated with a defined lifetime risk of breast (BC), ovarian (OC) and other cancers. Testing BRCA genes is pivotal to assess individual risk, but also to pursue preventive approaches in healthy carriers and tailored treatments in tumor patients. The prevalence of BRCA1 and BRCA2 alterations varies broadly across different geographic regions and, despite data about BRCA pathogenic variants among Sicilian families exist, studies specifically addressing eastern Sicily population are lacking. The aim of our study was to investigate the incidence and distribution of BRCA pathogenic germline alterations in a cohort of BC patients from eastern Sicily and to evaluate their associations with specific BC features.Patients and Methods: Mutational status was assessed in a cohort of 389 BC patients, using next generation sequencing. The presence of alterations was correlated with tumor grading and proliferation index.Results: Overall, 35 patients (9%) harbored a BRCA pathogenic variant, 17 (49%) in BRCA1 and 18 (51%) in BRCA2. BRCA1 alterations were prevalent among triple negative BC patients, whereas BRCA2 mutations were more common in subjects with luminal B BC. Tumor grading and proliferation index were both significantly higher among subjects with BRCA1 variants compared to non-carriers.Conclusion: Our findings provide an overview about BRCA mutational status among BC patients from eastern Sicily and confirm the role of NGS analysis to identify hereditary BC patients. Overall, these data are consistent with previous evidences supporting BRCA screening to properly prevent and treat cancer among mutation carriers.Keywords: hereditary breast cancer, BRCA1/2, NGS, tumor grading, Ki-67