A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer

Inclusion Criteria:

• Individuals 35-50 years of age, inclusive

• Patients who will undergo risk-reducing salpingo-oophorectomy (RRSO) (for the BSOarm) and patients who have declined or elected to defer BSO after proper counsellingto clearly explain the standard of care for BRCA1 mutation carriers and areundergoing salpingectomy (for the BLS arm with delayed oophorectomy arm).Concurrently planned hysterectomy with either arm is permitted

• At least one intact ovary and fallopian tube is in situ at the time of counseling,consent, and registration. Prior hysterectomy is allowed provided it did not includebilateral salpingectomy. Prior tubal ligation is allowed if one ovary and fallopiantube (with fimbria not removed) are present

• Positive Clinical Laboratory Improvement Act (CLIA)-approved test results forpathogenic or likely pathogenic germline BRCA1 mutation in the patient.Documentation of the result is required

• Patients may be premenopausal or menopausal

• Pelvic ultrasound (transvaginal imaging preferred, but transabdominal imaging isacceptable) and CA-125 within 180 days of registration

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry

• Individuals who are currently pregnant or plan to become pregnant in the futurethrough assisted reproductive technologies and who have received proper counselingare eligible. Individuals who are currently pregnant and plan bilateralsalpingectomy at the time of a planned cesarean section are eligible. Patients mustunderstand that they will not be able to become pregnant naturally in the future

Exclusion Criteria:

• Individuals with a history of any prior cancer who have received cytotoxicchemotherapy within the past 30 days or radiotherapy to abdomen or pelvis at anyprior time. Endocrine therapy or maintenance ERBB2/HER2 targeted therapy is allowed.Maintenance immune checkpoint inhibitor therapy is allowed. Maintenance therapy withPARP in inhibitor is allowed.

• Prior history of ovarian cancer, including low malignant potential neoplasms (LMP),primary peritoneal carcinoma, or fallopian tube carcinoma

• Patients medically unfit for the planned surgical procedure

• Patients with abnormal screening tests (pelvic ultrasound, CA-125) suspicious foroccult or gross pelvic malignancy within the past 180 days

• An abnormal pelvic ultrasound is defined as morphologic or structuralvariations suspicious for ovarian malignancy. Complex cystic lesions felt torepresent a benign lesion are not exclusionary. Simple cysts of any size arenot exclusionary

• An abnormal CA-125 is defined as a level > 50U/ml in premenopausal individualsif they are not current users of oral contraceptives; an abnormal CA-125 isdefined as a level > 40U/ml for premenopausal individuals who are current usersof oral contraceptives (Skates 2011). An abnormal CA-125 is defined as a level > 35 U/ml in postmenopausal individuals