Genetic and clinical characterization of BRCA-associated Hereditary Breast and Ovarian Cancer in Navarra (Spain)

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Abstract Background Genetic testing for BRCA1/2 genes is widely used as a strategy to reduce incidence and morbidity of hereditary breast and ovarian cancer. The purpose of this study is to analyse the demographic and molecular characteristics of BRCA germline mutations in Navarra, Spain, and to investigate the clinical profile of hereditary and sporadic breast cancer (BC) and ovarian cancer (OC) in the Community. Methods The study includes 1246 individuals assessed for BRCA1/2 genetic testing in Navarra, during 2000-2016, and a cohort of BC (n=4384) and OC (n=561) from the population-based Navarra Cancer Registry. Distribution and molecular characteristics of BRCA1/2 mutations, as well as, comparative analysis of the clinical course, pathologic features and overall survival of patients in different risk groups were investigated. Results BRCA mutation detection rate was 16%, with higher proportion (63%) of BRCA2 families. Nineteen per cent of mutations were recurrent, one of which, BRCA2 c.6024dupG, showed high association to OC. BRCA carriers had double risk (95% CI=1.04-4.33) of developing multiple malignancies than low risk families and were diagnosed at a much earlier age (16.6 and 11.7 years difference for BC and OC, respectively) when compared to the general population. For BC, BRCA carriers showed a more advanced histological stage, higher risk of bilateral neoplasms (OR=4.3; 95% CI=1.3-11.4, for BRCA2 carriers) and worse overall survival rate at 5-, 10- and 15- years, than women with sporadic tumors. For OC, over 70% of patients of all risk groups showed advanced stages at diagnosis, with the highest 91% among BRCA1 carriers (91%). Furthermore, they also had higher probability of developing bilateral tumors (OR=7.8, 95%CI=1.7-55.7) than the general population. Five-year overall survival rate was worse among women with sporadic OC than in BRCA carriers, but it levelled out over the 15-year period. Conclusions This study describes the molecular features of BRCA1/2 mutations in Navarra and defines the clinical course and outcomes of BRCA associated tumors compared with those of sporadic origin. Long term assessment of mortality and survival will be required to evaluate the impact of BRCA genetic testing program on the health of target population in our community.

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