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29.08.2018 | Epidemiology

A portrait of germline mutation in Brazilian at-risk for hereditary breast cancer

verfasst von: Ana Rafaela de Souza Timoteo, Ana Élida Menezes Magalhães Gonçalves, Lucas Amadeus Porpino Sales, Betina Menezes Albuquerque, Jorge Estefano Santana de Souza, Patrícia Cristina Pascoto de Moura, Marcos Alberto Arruda de Aquino, Lucymara Fassarela Agnez-Lima, Tirzah Braz Petta Lajus

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2018

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Abstract

Purpose

Knowledge about the germline mutational spectrum among Brazilian with hereditary breast and ovarian cancer (HBOC) is limited. Only five studies have performed comprehensive BRCA sequencing, corresponding to 1041 individuals among a Brazilian population of over 207 million people. Herein we aimed to determine the clinical and molecular characteristics of Brazilian patients who underwent oncogenetic counseling and genetic testing of a panel of high-risk and moderate-risk genes from 2009 to 2017.

Methods

Massively parallel sequencing was applied in 157 individuals (132 breast cancer-affected and 25 breast cancer-unaffected individuals) selected according NCCN criteria for hereditary breast cancer. Analysis of mutation segregation in family members was performed by capillary bidirectional sequencing, clinical response after treament and survival analysis was estimated by Kaplan–Meier.

Results

Nineteen germline variants were identified,15 pathogenic and 4 VUS (Variants of Uncertain Significance) in 27 individuals (27/157; 17% P < 0.0001) distributed among 7 genes. Sixty-eight percent of patients (13/19) harbor mutation in BRCA genes and 32% (6/19) in moderate risk genes. This is the first study reporting ATR deleterious germline mutation in association with hereditary breast cancer. Cancer-affected patients with moderate- risk mutation present a more aggressive phenotype, with bilateral cancer (25% vs. 13%, P = 0.0305), high-grade tumors (79.2% vs. 46.3%, P = 0.0001) and triple-negative (50% vs. 22.4%, P < 0.0001). However, no difference in the 5 years overall survival was observed between BRCA and moderate risk groups.

Conclusions

This work highlights the benefits of large-scale sequencing for oncogenetic counseling and extends our understanding about the genetics of hereditary breast cancer in the multi-ethnic Brazilian population.

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Titel: A portrait of germline mutation in Brazilian at-risk for hereditary breast cancer
verfasst von: Ana Rafaela de Souza Timoteo
Ana Élida Menezes Magalhães Gonçalves
Lucas Amadeus Porpino Sales
Betina Menezes Albuquerque
Jorge Estefano Santana de Souza
Patrícia Cristina Pascoto de Moura
Marcos Alberto Arruda de Aquino
Lucymara Fassarela Agnez-Lima
Tirzah Braz Petta Lajus
Publikationsdatum: 29.08.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4938-0

Springer Medizin

A portrait of germline mutation in Brazilian at-risk for hereditary breast cancer