Mutational spectrum of breast cancer susceptibility genes among women ascertained in a cancer risk clinic in Northeast Brazil

(1)Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

(2)Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz Bahia, Salvador, Bahia, Brazil.

(3)Centro de Investigação Translacional em Oncologia (CTO), Instituto do Cancer do Estado de São Paulo (ICESP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.

(4)Instituto D'or de Pesquisa e Ensino, Salvador, Bahia, Brazil.

(5)Department of Medicine, Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, Illinois, USA.

(6)Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.

(7)Universidade do Estado da Bahia, Salvador, Bahia, Brazil.

(8)Grupo Oncoclínicas, São Paulo, São Paulo, Brazil.

(9)Laboratório de Pesquisa em Infectologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

(10)Núcleo de Oncologia da Bahia, Salvador, Bahia, Brazil.

(11)Department of Medicine, Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, Illinois, 60637-1470, USA.

PURPOSE: There is a paucity of data on the spectrum and prevalence of pathogenic variants among women of African ancestry in the Northeast region of Brazil. METHODS: We performed BROCA panel sequencing to identify inherited loss-of-function variants in breast cancer susceptibility genes among 292 Brazilian women referred to a single institution cancer risk assessment program. RESULTS: The study included a convenient cohort of 173 women with invasive breast cancer (cases) and 119 women who were cancer-free at the time of ascertainment. The majority of the women self-reported as African-descended (67% for cases and 90.8% for unaffected volunteers). Thirty-seven pathogenic variants were found in 36 (20.8%) patients. While the spectrum of pathogenic variants was heterogeneous, the majority (70.3%) of the pathogenic variants were detected in high-risk genes BRCA1, BRCA2, PALB2, and TP53. Pathogenic variants were also found in the ATM, BARD1, BRIP1, FAM175A, FANCM, NBN, and SLX4 genes in 6.4% of the affected women. Four recurrent pathogenic variants were detected in 11 patients of African ancestry. Only one unaffected woman had a pathogenic variant in the RAD51C gene. Different risk assessment models examined performed well in predicting risk of carrying germline loss-of-function variants in BRCA1 and/or BRCA2 in breast cancer cases. CONCLUSION: The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations.