Risk of Ovarian Cancer Among Women With a Pathogenic Variant in BRCA1 According to Mutation Type and Location

Document Type

Conference Proceeding

Publication Date

2-2026

Publication Title

International Journal of Gynecological Caner

Abstract

Introduction/Background: Women carrying a pathogenic or likely pathogenic BRCA1 mutation face the highest lifetime risk of ovarian or fallopian tube cancer. This study aimed to estimate this risk according to mutation type and location in a cohort of BRCA1 carriers. Methodology: We identified 4,286 BRCA1 carriers, aged 30-74 years, with no prior ovarian/fallopian tube cancer, eligible for inclusion. These women were enrolled in a longitudinal study with biennial follow-up. Mutations were classified according to type and location. The 5-, 10- and 15-year cumulative ovarian cancer risks were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for ovarian cancer risk by mutation type and location. Results: During a mean follow-up of 7.2 years (range 0.0-15.0), 225 (5.2%) ovarian/fallopian tube cancers occurred. Mutations located within exon 10 were associated with a higher ovarian cancer risk, with a 15-year risk of 15.3% compared to 12.8% for those located outside (P=0.004). Mutations within exons 4—9 and 19—23 conferred a reduced risk compared to exon 10, with a HR of 0.53 (95%CI: 0.34-0.83) and 0.57 (95%CI: 0.41—0.80), respectively (P≤0.005). Cumulative ovarian cancer risks at 5, 10, and 15 years were 7.7%, 9.9%, and 15.3% for exon 10; 3.8%, 6.9%, and 13.5% for exons 4—9; and 4.0%, 7.8%, and 11.7% for exons 19—23, respectively. Missense mutations were associated with the lowest risk (HR 0.49; 95% CI 0.31-0.78; P≤0.003) compared to other mutation types. Among founder mutations (n=2,697, 62.9%), c.181T>G and c.5263_5264insC showed a reduced 15-year risk of 12%. Conclusion: Although there were some variations in cancer risk by type and location, the persistent elevated risks in all women with a pathogenic/likely pathogenic BRCA1 mutation reinforce the role of risk-reducing bilateral salpingo-oophorectomy. Integrating mutations into risk prediction models may enhance individualized risk assessment and guide future studies

Volume

36

Issue

2 Suppl 1

First Page

102899

Comments

ESGO (European Society of Gynaecological Oncology) 2026 Congress, February 26-28, 2026, Copenhagen, Denmark

Last Page

102899

DOI

10.1016/j.ijgc.2025.102899

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