Introduction/Background High-grade ovarian cancer (HGOC) is a heterogeneous disease. Homologous recombination proficiency (HRP) is often presumed in cases with genetic alterations such as CNNE1 amplification (CCNE1amp), loss of NF1, or loss of RB1. This study aims to evaluate their clinical outcomes. In addition, where available we described the HRD status (BRCAm and genomic instability score, GIS)

Methodology We conducted a retrospective analysis of patients with HGOC whose tumor benefited from NGS at Gustave Roussy in order to identify those harboring CNNE1amp, NF1 loss or RB1 loss. Clinical features, treatment history, survival outcomes, and HRD status were described for each of these 3 subgroups.

Results We identified 64 tumors with either a CCNE1amp (N=39), NF1 loss (N=18), or RB1 loss (N=7). 46.8% were stage III, 95% received neoadjuvant chemotherapy and 84% underwent surgery. Median overall survival was 117.9 months for CNNE1amp, 109 months for NF1 loss, and 97.6 months for RB1 loss (p=0.702). Among CCNE1amp tumors, no BRCAm were identified, however for those with GIS results available, 25% (3/12) were classified as HRD-positive. Among tumors with NF1 loss, 30% (6/18) had a deleterious BRCA1 or BRCA2m; a similar proportion (2/7) of tumors with RB1 loss had BRCA2m.

Conclusion CNNE1amp, NF1 loss, and RB1 loss are genetic alterations that are presumed to be associated with an HRD-negative status in HGOC. However, while CCNE1amp and BRCA1/2m were mutually exclusive, this was not the case for NF1 or RB1 loss, where a surprisingly high proportion (30%) of HGOC with NF1/RB1 loss harbored co-existing BRCA1/2m. Additionally 25% of CCNE1amp HGOC were classified as HRD on the basis of a high GIS. It is necessary to investigate the relationship between the alterations in CCNE1, NF1 or RB1 and HRD status/PARP inhibitor benefit, and validate cut-offs to define biologically relevant copy number changes for CCNE1, NF1 and RB1 in HGOC.

Disclosures Nothing