1582P - Pregnancy and miscarriage in epithelial ovarian cancer (EOC) patients harboring mutational signature of homologous recombination deficiency (HRD)

Background

Emerging evidence suggests that the defective homologous recombination repair (HRR) of DNA double-strand breaks (DSBs) in human trophoblast cells may induce spontaneous miscarriage (SM), as indicated by lower levels of BRCA1/RAD51 and higher levels of DSBs in villous tissue samples of recurrent SM. Furthermore, cancer therapies can induce DNA damage not only in cancer cells but also in healthy cells, including oocytes. Oocytes have the capacity to repair DSBs during meiosis. DNA damage in oocytes induces meiotic errors, leading to abnormalities and increased susceptibility to SM.

Methods

This was a real-world, hospital-based, study, including EOC patients undergoing BRCA1/2 tumor (t), germline (g), and genomic instability testing between May 2015 and May 2024. In the current analysis we investigate cumulative incidence of pregnancy and miscarriage according to BRCA1/2 mutational status (presence/absence of t/g (likely)pathogenic variants, PVs), and HRD status (HRD positive/negative) assessed by myChoiceCDx/SOPHiA DDM™ assays. Patients carriers of PVs in HR no-BRCA1/2 genes were excluded.

Results

Six hundred and thirty-five (635) EOC patients were included in the analysis: 130 were carriers of gPVs in BRCA1/2 genes (20.5%): 86 in BRCA1 (66.1%) and 44 in BRCA2 (33.9%); while 33 showed tPVs (5.2%). Of the 135 samples analyzed by the HRD genomic instability test, 51 (37.8%) were identified as HRD-positive, and 69 (51.1%) as HRD-negative. When the cumulative incidence of pregnancy between the groups was compared, the difference was not significant. Notably, HRD-positive EOC patients showed a statistically significant increase in miscarriage, compared to patients in the HRD negative subgroup (31.1% vs 12.1%, respectively; p=0.02).

Conclusions

Our data suggested that pregnancy in EOC patients with HRD positive tumors is associated with increased incidence of miscarriage. Prospective validation of these findings is required. Meanwhile, oncofertility counseling, and a more in-depth assessment of risk factors, could be proposed to optimize abortion risk-management and improve fetal and obstetric outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.