Introduction/Background Risk Reducing Salpingo-Oophorectomy (RSSO) is the main prophylactic option in BRCA-mutated patients. Current evidence indicates that the first step in the carcinogenetic process is TP53 gene mutation, resulting in tubal alterations ranging from p53 signature to serous tubal intraepithelial carcinoma (STIC), via serous tubal intraepithelial lesion (STIL), to high-grade serous ovarian carcinoma (HGSC). The aim of our study is to evaluate the role of different BRCA mutation types on the age of onset of tubal histopathological abnormalities after RRSO.

Methodology Women with known germline pathogenic mutation to BRCA1/2 genes who underwent RRSO at San Raffaele Hospital, Milan, between November 2012 and May 2023, were considered in this analysis. Histopathological analysis was carried out by expert pathologists using standardized definitions for tubal abnormalities. Patients were assessed according to mutation type in BRCA1/2 genes: frameshift, missense, nonsense and splicing.

Results A total of 65 patients were included, 38 (58.5%) BRCA1 and 27 (40.9%) BRCA2 mutation carriers. P53 signature was reported in 28 patients, while STIL and STIC/Cancer in 12 and 7 patients respectively. Frameshift was the most frequent mutation type in all subgroups (n=35, 52.6%). We observed an older age of onset in the group of frameshift mutation carriers with respect to non-sense mutation carriers (48.9 VS 43 years in the BRCA2-mutated p53 signature group; 62.3 VS 45.5 years in the BRCA1-mutated STIC/Ca group).

Conclusion Recent evidence suggests that BRCA1/2 nonsense mutation carriers present younger age of onset of HGSC compared to frameshift mutations. Data from our study confirm this trend also for the onset of tubal abnormalities. Due to the small sample size, this finding was not statistically significant. If confirmed, on a larger scale, more personalized management for the risk-reducing strategies in BRCA1/2 women might be introduced.

Disclosures The authors declare no conflict of interest.