Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis
Open Access
- 19 February 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 16 (2), e0247363
- https://doi.org/10.1371/journal.pone.0247363
Abstract
Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2, 8 (3.5%) TP53, 1 (0.5%) PALB2. Moderate penetrance genes (ATM, CHEK2) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (pBRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population.This publication has 51 references indexed in Scilit:
- Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based TestingJNCI Journal of the National Cancer Institute, 2014
- Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patientsGenetics in Medicine, 2014
- Germline mutations in BRCA1, BRCA2, CHEK2 and TP53 in patients at high-risk for HBOC: characterizing a Northeast Brazilian PopulationHuman Genome Variation, 2014
- Prevalence of the TP53 p.R337H Mutation in Breast Cancer Patients in BrazilPLOS ONE, 2014
- Hereditary breast and ovarian cancer: assessment of point mutations and copy number variations in Brazilian patientsBMC Medical Genetics, 2014
- Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjectsBMC Medical Genetics, 2014
- CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian familiesArquivos de Gastroenterologia, 2012
- Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern BrazilGenetics and Molecular Biology, 2009
- Genetic epidemiology of BRCA mutations – family history detects less than 50% of the mutation carriersEuropean Journal of Cancer, 2007
- The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian familiesCancer Letters, 2007