Pregnancy and miscarriage before epithelial ovarian cancer (EOC) diagnosis in patients carrying germline <i>BRCA1/BRCA2</i> pathogenic variants.

Abstract

e22516 Background: Several case-control studies have been performed to understand the prognostic impact of pregnancy after breast cancer in patients carrying germline BRCA1/2 (g BRCA1/2 ) pathogenic/likely pathogenic variants (PVs). The median age of onset of epithelial ovarian cancer (EOC) diagnosis is higher than breast cancer. Clinical data on fertility, pregnancy outcomes, and abortion rates before the EOC onset are still missing. Previous research showed that g BRCA PV carriers may have a reduced ovarian reserve, earlier menopause than the general population, and defective homologous recombination repair of DNA double-strand breaks in human trophoblast, potentially leading to spontaneous miscarriage. Methods: This was a real-world, hospital-based cohort study to assess the cumulative incidence of pregnancy and miscarriage in a consecutive series of EOC patients who underwent g BRCA1/2 between May 2015 and December 2024. EOC patients carrying PVs in no- BRCA1/2 genes or tumor BRCA1/2 PVs were excluded from the current analysis. Results: From May 2015 to December 2024, 731 EOC patients were included in the analysis: 138 were carriers of g BRCA1/2 PVs (18.9%): 93 in BRCA1 (67.4%), and 45 in BRCA2 (32.6%). The number of patients with at least 1 pregnancy, abortion included, was 91 in the g BRCA carriers vs 192 in the g BRCA non-carriers. Notably, when the incidence of miscarriage between BRCA carriers and non-carriers was compared, the reduced incidence of spontaneous miscarriage was in the group of patients carrying g BRCA PVs [ BRCA carriers vs non-carriers: 11/92 (12.1%) vs 51/192 (26.6%)]. The total number of full-term pregnancies was 205 for g BRCA carriers vs 192 for non-carrier patients. Also, the median number of full-term pregnancies for single patients was higher in the patients harboring g BRCA PVs vs BRCA wild type (2.25 vs 1.5). The total number of miscarriages was 20 among g BRCA carriers vs 70 among non-carriers, with a lower miscarriage rate for individual patients in the BRCA -mutated patients (1.8 vs 1.3). The genetic characteristics and the EOC clinical behavior between parous and nulliparous women, according to BRCA mutational status, were also collected. Conclusions: Genetic diagnosis of constitutional BRCA1/2 PVs mutation raises concerns about the future fertility of female carriers. Interestingly, our data suggested that pregnancy in EOC women carriers of g BRCA1/2 PVs was associated with a reduced incidence of miscarriage than non-carriers. Prospective validation of these findings is required to improve understanding of fetal and obstetric outcomes and to guide counseling for BRCA carrier patients.