HEREDITARY BREAST CANCER IN THE STATE OF CEARÁ (THE CHANCE COHORT)

Introduction: The identification of Hereditary Cancer Predisposing Syndromes (HCPS) and its genetic variants in Brazilian populations is an unmet need to improve our Breast Cancer prevention and treatment policies. Cancer patients can benefit from early screening, genetic counseling, preventive procedures and treatment choices. As a multiethnic and continental country, Brazilian epidemiological knowledge of most common pathogenic variants in each region can contribute to better public health strategies aimed to optimize cancer care to specific populations. Purpose: Considering the deficit of epidemiological studies involving HCPS, especially in the Northeast region of Brazil, it is essential to identify and assess the prevalence of mutational variants in patients susceptible to hereditary breast cancer in Ceará. Methods: From march 2014 to december 2020, the prospective cohort study included patients aged over 18 years and referred to CHANCE Group (Grupo de Câncer Hereditário do Ceará). Probands at the discretion of one individual per family were included as per the National Comprehensive Cancer Network (NCCN) breast cancer susceptibility genes molecular testing criteria restricted to those born in the state of Ceará. Genetic material was collected from saliva or blood samples and sent for multigenic panels to College of American Pathologists-certified laboratories. At least 30 cancer predisposition genes were analyzed. Results: A quantitative cut of 355 patients was included in the study, among the 736 referred to CHANCE. In this sample, 97 (27.3%) had pathogenic or likely pathogenic (P/LP) germline variants in 18 different genes, including high penetrance genes – BRCA1 (8.7%), BRCA2 (7.0%) PALB2 (2.8%) – and low/ moderate penetrance genes – CHEK2 (1.9%), ATM (1.1%), BARD1 (0,56%), RAD51C (0,28%) and RAD51D (0,28%). Genes lacking unequivocal association with breast cancer predisposition corresponded to 4.2% of P/LP variants, in contrast to the surprisingly low prevalence of TP53 (0.28%). Conclusion: In this representative study population of Ceará, the prevalence of P/LP germline variants was high as compared to other Brazilian and Northeast region cohorts, although the frequency of some genes was mitigated in relation to what was expected. The description of more detailed mutational profiles and involved genes, through the access to genetic counseling and molecular diagnosis may bring better Breast Cancer management to patients and families in Ceará.