RESUMEN
Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.
Asunto(s)
Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Proteína p53 Supresora de Tumor , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Brasil/epidemiología , Adulto , Proteína p53 Supresora de Tumor/genética , Persona de Mediana Edad , Pruebas Genéticas/métodos , Salud Pública , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiología , AncianoRESUMEN
Precision medicine has provided new perspectives in oncology, yielding research on the use of targeted therapies across different tumor types, regardless of their site of origin, a concept known as tissue-agnostic indication. Since 2017, the Food and Drug Administration (FDA) has approved the use of three different agents for tumor-agnostic treatment: pembrolizumab (for patients with microsatellite instability or high tumor mutational burden) and larotrectinib and entrectinib (both for use in patients harboring tumors with NTRK fusions). Importantly, the genomic alterations targeted by these agents are uncommon or rare in breast cancer, and little information exists regarding their efficacy in advanced breast cancer. In this review, we discuss the prevalence of these targets in breast cancer, their detection methods, the clinical characteristics of patients whose tumors have these alterations, and available data regarding the efficacy of these agents in breast cancer.
RESUMEN
A análise da validade ética das pesquisas se concretiza nos Comitês de Ética em Pesquisa (CEP) das instituições. Este trabalho apresenta o histórico de organização e implementação do Comitê de Ética em Pesquisa na Universidade Federal de Santa Maria (UFSM), a demanda de análise de projetos e divulga a sua importância na universidade. Os dados foram obtidos através de um levantamento histórico realizado pela análise de arquivos internos do CEP. Foi pesquisado o número de projetos submetidos à avaliação pelo CEP desde sua fundação até dezembro de 2009, assim como de seu local de origem.
The analysis of the ethical validity of research materializes in the Research Ethics Committee (CEP) of institutions. The objective of the present article was to briefly present the history of the organization and implementation of the Research Ethics Committee at Universidade Federal de Santa Maria (UFSM), as well as the trends in demand for project analysis, in addition to disclosing its importance to the institution. Data were collected by means of a historical research based on the analysis of internal files of the CEP. We investigated the number of projects submitted for review by the CEP from its implementation to December 2009.