Molecular Characterization of Hereditary Breast and Ovarian Cancer Patients from a Public Precision Medicine Service in the Southeast Brazilian Population

Introduction: In the southeast of Brazil, we established a Hereditary Cancer Predisposition Assessment and Family Monitoring Program to support patients and families with hereditary cancer syndromes. The program was built around the development of a patient care flowchart to guide follow-up strategies, employing a highly specialized team that included genetic counseling, psychological support, and advanced molecular diagnostic techniques, targeting patients within the public health system. Methods: Genetic screening of genes associated with the syndrome was conducted on 210 Brazilian patients using Sanger sequencing and NGS technology. Results: Pathogenic or likely pathogenic mutations were identified in 33.3% (70/210) of patients, with 14.3% (30/210) harboring mutations in non- BRCA genes. The most prevalent pathogenic mutation identified was c.4829_4830delTG in the BRCA2 gene, with a prevalence of 8.5% among the identified mutations. This mutation seems to be very rare in other cohorts of Brazilian breast/ovarian patients. Additionally, 8.4% of the analyzed individuals exhibited P/LP variants in genes related to other hereditary cancers. Thirteen variants across nine genes, identified for the first time in Brazil, are presented here. Forty-one variants of uncertain significance were found, distributed across 12 different genes, with the majority (8/41, 19.5%) observed in the ATM gene. Conclusion: This study represents the first investigation focused on patients from the Brazilian public health system in the Southeast Brazilian population. By identifying pathogenic mutations in these patients, precision medicine care can be implemented, leading to improved care for patients and their families.