BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, Ovarian Cancer, RAD51C Gene Mutation, RAD51D Gene Mutation
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDURERisk-reducing salpingectomy with delayed oophorectomy
* BRCA1: RRS at age 25-40 and RRO at a maximum age of 45 (advised between 35 and 45). * BRCA2: RRS at age 25-45 and RRO at a maximum age of 50 (advised between age 40 and 50). * BRIP1, RAD51C, RAD51D: RRS at age 25-50 and RRO at a maximum age of 55 (advised between 45 and 55)
PROCEDURERisk-reducing salpingo-oophorectomy
* BRCA1 at a maximum age of 40 (advised between age 35 and 40) * BRCA2 at a maximum age of 45 (advised between age 40 and 45) * BRIP1, RAD51C, RAD51D: at a maximum age of 50 (advised between 45 and 50)
Sponsors
University Medical Center Nijmegen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High grade serous (ovarian) cancer incidence | Until the age of 45 for BRCA1 and 50 for BRCA2 germline mutation carriers | High grade serous (ovarian) cancer incidence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of (pre)malignant findings in tubes/ovaries | 6 weeks after each surgery | Incidence of (pre)malignant findings in tubes/ovaries at risk-reducing salpingectomy, oophorectomy and salpingo-oophorectomy. |
| Peri-operative morbidity and mortality | 6 weeks after each surgery | Peri-operative morbidity and mortality |
| Incidence of pelvic cancer (other than ovarian cancer) | Up to the age of 70 | Incidence of pelvic cancer (other than ovarian cancer) |
| Incidence of breast cancer | Up to the age of 70 | Incidence of breast cancer |
| Uptake of risk reducing oophorectomy | Up to the age of 70 | Uptake of risk reducing oophorectomy after risk reducing salpingectomy |
Countries
Australia, Austria, Belgium, Brazil, Canada, Germany, Ireland, Italy, Mexico, Netherlands, Norway, Poland, Spain, Sweden, United States, Uruguay
Contacts
CONTACTJoanne A. de Hullu, MD, PhD
CONTACTKaren H. Lu, MD, PhD
PRINCIPAL_INVESTIGATORJoanne A. de Hullu, MD, PhD
Radboud University Medical Center
PRINCIPAL_INVESTIGATORKaren H. Lu, MD, PhD
M.D. Anderson Cancer Center
PRINCIPAL_INVESTIGATORRosella P.M.G. Hermens, MD,PhD
Radboud University Medical Center
PRINCIPAL_INVESTIGATORElizabeth M. Swisher, MD, PhD
University of Washington
Outcome results
None listed