747 Ovarian cancer onset across different BRCA mutation type

Introduction/Background* Mutations in BRCA-genes have been identified as predisposing to hereditary breast and ovarian cancers. Little is known about how ovarian cancer risks differs across different BRCA mutation type. The purpose of our study is to identify the correlation between specific type of BRCA mutations and (1) age of onset of high-grade serous ovarian cancer (HGSOC) and (2) patients’ survival. Methodology Retrospective multicentric series of newly diagnosed HGSOC-patients with FIGO Stage III-IV, assessed for germline (g)BRCA status. BRCA gene mutations were classified into 5 groups: deletion, insertion, no-sense, missense and splicing. Result(s)* A total of 214 patients were included in the analysis. 143 (67.1%) had a gBRCA1-pathogenic variant (PV) and 71 (33.1%) had a gBRCA2-PV. Overall, the mean age of onset was 54.75 years (10.9 SD) with a difference of around 4 years between patients having BRCA 1 and BRCA2 mutations (53yrs, SD 10.9 vs. 57.2yrs, SD 10.5; p=0.018). The most frequent mutation found was deletion (42.9%). Patients with no-sense mutation (18.2%) had the youngest age of onset, both in BRCA1 and BRCA2 subgroups, with an earlier occurrence of around 6 and 4 years respectively (BRCA1 group: 48.8yrs, SD 9.7 vs.54.7yrs, SD10.9; p=0.008) (BRCA2 group 53.0yrs SD 5.5 vs. 57.9yrs SD 10.9; p=0.04). Women with insertion (18.7%) had the oldest age of onset, both in BRCA 1 (57.7yrs, SD 11.7 vs. 52.2yrs, SD10.6; p=0.028) and BRCA2 (59.6yrs SD 10.1 vs. 56.6yrs SD 10.6) subgroups (p=ns) (table 1). No statistically significant difference in overall survival was found among the 5 groups examined (figure 1). Conclusion* Our study highlights for the first time that different types of BRCA mutations could indicate a different age for OC onset. If confirmed in larger series, it might have a relevant clinical impact, leading to a more tailored approach for risk-reducing surgery strategies for OC prevention. Moreover, as we initially include only advanced stages in our analysis, further investigation on the time of onset of early BRCA mutated OC is currently ongoing.