TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

The aim of the project is to evaluate the risk-reducing salpingectomy with delayed oophorectomy as an alternative for risk-reducing salpingo-oophorectomy in high risk women with respect to ovarian cancer incidence.

In BRCA1/2 gene mutation carriers, a risk-reducing salpingo-oophorectomy (RRSO) is recommended around the age of 40. This recommendation is based on a 10-40% life-time risk of ovarian cancer in this population and disappointing results of ovarian cancer surveillance for early detection. Moreover, the mortality rate of ovarian cancer is high. Effects of RRSO are a decrease in ovarian cancer risk (80-96%) on one hand and immediate onset of menopause and non-cancer related morbidity on the other hand. The fifty percent breast cancer risk reduction after RRSO has become disputable in the last years. Based on multiple studies showing that most high-grade serous ovarian cancers develop at the distal end of the Fallopian tube, an innovative strategy for RRSO has been developed for this study proposal: risk-reducing salpingectomy (RRS) with delayed risk-reducing oophorectomy (RRO). However, the safety of this strategy has not been proven yet. Before implementing this innovative strategy as standard care we need to investigate the long term effects on ovarian cancer incidence.

Inclusion Criteria: * Women with a class 5 (definitely pathogenic) BRCA1, BRCA2, RAD51C, RAD51D or BRIP1 germline mutation in one of the participating centers. * Age at inclusion; * BRCA1: 25-40 years * BRCA2: 25-45 years * RAD51C, RAD51D, BRIP1: 25-50 years * Childbearing completed * Presence of at least one fallopian tube * Participants may have a personal history of non-ovarian malignancy * Informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution. Exclusion Criteria: * Postmenopausal status (natural menopause or due to treatment) * Wish for second stage RRO within two years after RRS * Legally incapable * Prior bilateral salpingectomy * A personal history of ovarian, fallopian tube or peritoneal cancer * Current diagnosis or treatment for malignant disease