[Clinical and familial characterisation of ovarian cancer patients with germline mutations in the BRCA1/2 gene and the current status of prevention in high-risk groups].

Objective: To analyze the clinical characteristics of breast cancer susceptibility gene (BRCA) germline mutation carriers with ovarian cancer, collect family history information, screen for potential BRCA mutation carriers among family members, and provide preventive guidance for high-risk populations of ovarian cancer. Methods: A total of 77 patients with ovarian cancer (including fallopian tube cancer and primary peritoneal cancer, hereinafter collectively referred to as ovarian cancer) who were treated at the Department of Obstetrics and Gynecology, Chinese PLA General Hospital between 2015 and 2024 and confirmed to carry germline mutations in the BRCA1/2 genes through genetic testing were selected. According to the test results, they were divided into the BRCA1 mutation group (48 cases) and the BRCA2 mutation group (29 cases). The clinical baseline data, pathological characteristics, treatment efficacy, and survival outcomes were compared between the two groups. Family history information was collected, and BRCA genetic testing was performed on 81 relatives from 37 families. Family characteristics were analyzed in combination with family history and genetic testing results, and preventive guidance was provided to high-risk populations. Results: The age at onset of the 77 patients ranged from 19 to 78 years, with a median age of 55 years. The age at onset in the BRCA1 mutation group ranged from 19 to 74 years, with a median age of 52 years, which was earlier than the median age of 56 years in the BRCA2 mutation group. 43.8% (21/48) of BRCA1 carriers had a family history of hereditary breast and ovarian cancer syndrome (HBOC), which was 1.5 times higher than that in the BRCA2 group (17.2%, 5/29, P＜0.05). There were no statistically significant differences in fertility status, body mass index (BMI), personal history of breast cancer, and pre-treatment carbohydrate antigen 125 (CA125) levels between the two groups (P＞0.05). The median progression-free survival (PFS) for initial treatment was 21.8 months in BRCA1 mutation patients and 20.7 months in BRCA2 mutation patients. Among the 81 relatives, 47 BRCA gene mutation carriers were detected, of whom 63.8% (30/47) were from families without a family history of HBOC. Among 31 female mutation carriers, only 2 underwent risk-reducing salpingo-oophorectomy (RRSO). A survey of the general population showed that 78.5% of non-carrier women would accept prophylactic surgery, while the average surgical intention score among carriers was only 2.6 (on a 5-point scale), with 75.0% preferring to delay RRSO until after natural menopause. Conclusions: Chinese BRCA1/2 mutation carriers have significant concerns regarding iatrogenic menopause caused by RRSO, creating a decision-making dilemma for surgical prevention of ovarian cancer in high-risk populations. The age at onset of ovarian cancer in Chinese BRCA1/2 mutation carriers is relatively late compared with international data, and the optimal timing of surgery for Chinese women still requires further investigation. Developing a localized surgical timing prediction model may help advance ovarian cancer prevention and treatment efforts.