Sequencing analysis of germline breast cancer mutations in Brazilian population

Abstract

Aims: Next-generation sequencing (NGS) allows sequencing the wide variety of cancer susceptibility genes. Hereditary breast cancer (BC) is found in 5 to 10% of the cases. Germline mutations are associated with the development of BC in younger women. The aim of this work is to describe germline mutations found in young Brazilian patients diagnosed with BC. Methods: DNA samples of peripheral blood cells from 32 young patients (<45 years) submitted to neoadjuvant therapy with no family history of BC were sequenced for the exons of 16 genes related to hereditary BC. Pathogenic mutations were analyzed based on known databases. Results: Pathogenic mutations were identified in 5 patients. Two patients were BRCA1 (6%), one BARD1 (3%) mutated, one patient (3%) harbours mutations in both genes and another has BARD1 and BRIP1 mutations (3%). BRCA1 mutations were only detected in Triple Negative (TN) patients, including one with BARD1 mutation. Two of them presented pathologic partial response (one with and another without relapse after two years). Luminal A patients analysis detected BARD1 mutation (pathologic complete response) and another with BRIP1 and BARD1 mutations (relapse after two years). Variants not yet described were found in three HER2 patients: two with pathologic partial response (BRCA2 and CHEK2) and one with pathologic complete response (NBN). Conclusions: Mutations in BRCA1 were related to TN subtypes of BC. Pathologic complete response was not detected in patients with only BRCA1 mutations. This study may contribute to the screening of germline mutations in patients with BC in Brazil.