Abstract
BACKGROUND/OBJECTIVE: BRCA1 and BRCA2 genes contain functional domains that operate at different stages of the DNA damage response. Although studies have suggested that the location of BRCA1/2 mutations may influence clinical outcomes, no discernible pattern has been observed indicating which mutation location influences clinical outcomes in patients with ovarian cancer with BRCA1/2 mutations. Therefore, this study aimed to evaluate the differences in survival outcomes between BRCA1/2 mutation locations, with a specific focus on exon 11, in patients with epithelial ovarian cancer. METHODS: A comprehensive literature review was conducted using PubMed, Embase, and Cochrane Library databases, including articles published up to 13 August 2024. Progression-free survival (PFS) and overall survival (OS) were assessed based on the BRCA mutation location, with subgroup analyses focusing on exon 11 mutations in BRCA1 and BRCA2. Statistical heterogeneity was evaluated using the I(2) index. RESULTS: Seven studies involving 1535 patients were included. BRCA2 exon 11 mutations demonstrated a significant PFS advantage (HR, 0.586; 95% CI, 0.346-0.994, I(2) = 55%), whereas BRCA1 exon 11 mutations had no significant effect on PFS or OS. CONCLUSIONS: These findings suggest differential prognostic outcomes based on the BRCA mutation location, highlighting the clinical relevance of BRCA2 exon 11. BRCA2 exon 11 mutations were associated with improved PFS, which underscores the prognostic significance of the BRCA mutation location, particularly exon 11, in ovarian cancer. These findings reinforce the biological relevance of exon 11 by consolidating evidence from multiple studies that suggest potential prognostic implications of mutations within this region.