Prevalence & pathogenic features of hereditary breast/ovarian cancer syndromes: Implementation of a genetic/familiar cancer risk assessment unit.

Abstract

e13645 Background: Currently studies found more than 25 genes associated with inherited Breast/Ovarian cancer. This syndrome shows morphologic, immunophenotic and molecular differences in comparison with sporadic ones. For example, BRCA1/2 are commonly ductal invasive carcinomas, with high grade of differentiation and high mitotic index, showing expression of basal o myoepithelial markers and overexpression of cell cycle proteins. Our study describe the outcomes since the implementation of Genetic/Familiar cancer risk assessment a tertiary hospital. Methods: A retrospective chart review was performed among all patients evaluated in Genetic counseling clinic in our hospital, since September 2008 to March 2019. Patients who fulfill criteria for Breast/Ovarian Cancer syndromes were included. We were specially interested in those with pathogenic, likely pathogenic or uncertain significance variants. All variants were named according to the practice of the BIC database, and the GenBank entries. Description on clinical features of tumor and frequency of implicated genes are considered for statistical analysis. All data were calculated in Stata IC 15. Results: 320 patients were eligible, 62,2% (n = 199) had cancer diagnosis. The most frequent tumor diagnosis was breast, 68,8% (n = 137), featured by: ductal carcinoma (82,5%), high grade differentiation (55,2%), triple negative (22,6%), local/locally advanced stage (86,13%) and bilateral component (16,1%). 11,6% had Breast cancer and 3,4% Ovarian cancer as second malignancies, respectively. Variant alterations were found in 24 different genes. BRCA 2 had the highest frequency (40,9%; n = 139 variants detected), BRCA 1 (24,7%; n = 84), ATM(7,4%; n = 25), PALB2(5,3%;n = 18) and BRIP1(2,9%, n = 10). 230 variants (68,3%) were pathogenic or likely pathogenic variants. Pathogenic mutation variant distribution in BRCA2 were c.3264dupT (n = 12); c.6275_6276delTT (n = 8); c.9026_9030delATCAT (n = 8). The most frequent mutations in BRCA1 were: c.1674delA (n = 7); c.302-1G > A (n = 4); c.3331_3334delCAAG(n = 4). Among all patient with BRCA 1/2 mutations, 30,7% were undergone to prophylactic surgery, without statistical association with survival (p = 0,310). Conclusions: Our findings support literature about highly relation between BRCA1/2 and Breast/Ovarian Cancer. In our population, BRCA2 showed high frequency of pathogenic mutations. Patients with BRCA mutations and prophylactic mastectomy did not show statistical benefit in survival.