Dados do Resumo

Título

FREQUENCY OF BRCA1 AND BRCA2 MUTATIONS IN TRIPLE NEGATIVE AND LUMINAL B BREAST CANCER IN A REGISTER OF THE PUBLIC HEALTH SYSTEM IN NORTHEAST BRAZIL

Introdução

BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers are at high risk of early-onset breast cancer and have an increased sensitivity to platinum-containing agents and poly(ADP-ribose) polymerase (PARP) inhibitors . Brazil, as a continental country, does not have accurate data on BRCA1 and BRCA2 mutations in cases of Triple-negative and Luminal B breast cancer.

Objetivo

the present study aimed to screen the BRCA1/2 genes for point mutations through next generations sequencing in 24 patients suspected of Hereditary Breast and Ovarian Cancer with triple negative and Luminal tumors.

Métodos

A retrospective analysis of the medical records of 600 patients with breast cancer from the Hospital São Marcos-Teresina registry was carried out to outline the epidemiological profile of breast cancer in the state of Piauí and identify patients with clinical criteria for Hereditary Breast and Ovarian Cancer. After selection, 24 women with breast cancer treated by the single health system, diagnosed between 2019 and 2023, were selected, with higher criteria for genetic testing by the NCCN guideline. A peripheral blood sample (2 mL) was collected from each participant and collected in a tube containing EDTA as an anticoagulant. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit according to the manufacturer's instructions. A single NGS platform, MiSeq Illumina, was adopted for the detection of small indel and single nucleotide variants. All coding exons of the BRCA genes were amplified using the AmpliSeq library (ethics committee approval number: CAAE: 38100920.2.1001.5214).

Resultados

The majority of patients had Triple negative (TN) (18 cases) and Luminal B (4 cases) tumors. Of the 18 TN cases, 4 had a known pathogenic mutation and 1 had a truncated (nonsense) probably pathogenic variant; and of the 4 Luminal B cases, one had a pathogenic mutation and two unrelated probands had the same inframe probably pathogenic variant. The overall mutation frequency was 33%, including 26% (5/19) for TN and 60% (3/4) for luminal B. The majority of patients (54.2%) reported a family history of cancer. The overall mean age of BC diagnosis was 35,8 (26-51) years old. From the TNBC cases, the mean age of diagnosis was 34.5 (26-41) yo and, of the TNBC mutation carries, the mean age o diagnosis was 34.5 (26-40) yo. From the Luminal B cases, the average BC diagnosis was 37 (33-40) yo and, for the Luminal mutation carries the average was 42 (36-51) yo.

Conclusões

The implementation of genetic sequencing significantly changes patient management in an oncology reference center in Northeast Brazil. The personalized approach based on genetic data has promoted better monitoring and prevention strategies for reducing breast cancer mortality such as prophylactic surgeries.

Financiador do resumo

FAPEPI (Fundação de Amparo a Pesquisa do Estado do Piauí - EFP_00020639 ) and CNPq

Palavras Chave

BRCA1; BRCA2; NGS