Radical Fimbriectomy for Young BRCA Mutation Carriers

Study Overview
=================
Brief Summary
-----------------
Some BRCA-mutated women are reluctant to undergo laparoscopic bilateral salpingo-oophorectomy. The goal of the bilateral laparoscopic radical fimbriectomy the investigators suggest, is to suppress the tubal source of possible dysplastic cells from which can stem this high grade tumor, while preserving a natural ovarian hormonal secretion.

Detailed Description
-----------------
Most of ovarian carcinomas related to BRCA 1 or 2 mutations are of fallopian tube origin and especially from its distant part called the fimbria. These tubal, ovarian or primary peritoneal carcinomas are quite always of high grade serous type. They cannot be effectively screened due to the quickness of their evolution. In this context, a laparoscopic bilateral salpingo-oophorectomy (BSO) is the recommended prophylactic procedure. Some BRCA-mutated women are reluctant to undergo this procedure considering the numerous adverse effects on body and quality of life, especially when hormonal replacement is forbidden. This refusal makes them at risk of developing a serous pelvic carcinoma. The goal of the bilateral laparoscopic radical fimbriectomy the investigators suggest, is to suppress the tubal source of possible dysplastic cells from which can stem this high grade tumor, while preserving a natural ovarian hormonal secretion

Official Title
-----------------
Radical Fimbriectomy for Young BRCA Mutation Carriers at Risk of Pelvic Serous Carcinoma

Conditions
-----------------
BRCA1 Mutation, BRCA2 Mutation, Hereditary Breast and Ovarian Cancer

Intervention / Treatment
-----------------
* Procedure: Radical fimbriectomy
* Other: Histopathology SEE-FIM


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Woman aged over 35 years When project of childbearing is fulfilled With a BRCA 1 or 2 mutation, or a family history of breast/ovarian cancer Unprepared to undergo bilateral annexectomy With or without breast cancer Patient affiliated to health insurance Dated and signed informed consent Exclusion Criteria: Menopausal woman defined as : Bilateral oophorectomy without hysterectomy and amenorrhea more than 12 months and/or FSH> 20 UI/l History of hysterectomy and FSH> 20 UI/l Pregnant or breastfeeding woman

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BRCA mutation carriers<br>Women with BRCA1 or BRCA 2 mutation or a family history of breast/ovarian cancer. Radical fimbriectomy. Histopathology SEE-FIM | Procedure: Radical fimbriectomy<br>* Laparoscopic bilateral radical fimbriectomy : Complete resection of the tubes, from the uterine tube (up against the uterus) to the fimbriae, with resection of the part of the ovary adjacent to the ovarian fimbriae (adhering to the ovary)<br>Other: Histopathology SEE-FIM<br>* Anatomopathological study of surgical specimens<br>* Other names: Sectioning and Extensively Examining the FIMbria;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pelvic cancer | Number of ovarian or primary serous peritoneal carcinoma occuring between fimbriectomy and menopause | an expected average of 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity associated with the radical prophylactic fimbriectomy | Morbidity will be assessed according to the Clavien-Dindo classification up to 30 days after the procedure and according to the NCI-CTCAE v4.0 grading scale beyond that time | Up to 30 days after the surgery | 
| Rate of occult lesions on fimbriectomy specimens and secondary oophorectomy specimens | Number of serous tubal intraepithelial carcinoma or invasive carcinomas on the operative specimens | Within 1 month after fimbriectomy, and within 1 month after oophorectomy | 
| Incidence of breast cancer on patients without breast cancer before fimbriectomy, and incidence (de novo or recurrence) of breast cancer on the overall study population | Number of cases of breast cancer or breast cancer recurrence observed | an expected average of 15 years | 
| Rate of secondary oophorectomies and associated morbidity, and reasons for oophorectomy if decided before the age of 50 et before menopausis | Number of oophorectomies and time between fimbriectomy and oophorectomy Complications according to NCI-CTCAE v4.0 grading scale | an expected average of 15 years | 
| Proteomic profile of tissues from radical fimbriectomy | Immunostaining is realised on sections of ovary portion, fimbriae and fallopian tubes, then tumoral zones are selected for spatially resolved gun microproteomic analysis | Up to 7 years after sample collection | 
| Proportion of menopausal women before oophorectomy or at the LPLV without oophorectomy, and rate patients who experienced early menopause (before the age of 40) | Number of cases of menopausis an early menopausis observed | an expected average of 15 years | 
| Proportion of benign histological abnormalities on radical Fimbriectomy specimens | Number of benign histological abnormalities on the operative specimens | Within 1 month after fimbriectomy | 
| Patient's satisfaction at distance from Radical Fimbriectomy | Patient satisfaction survey | Up to 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BRCA1, BRCA2, Prophylactic surgery, Salpingectomy, Fimbriectomy