Problems raised by the gynaecologic management of women with BRCA 1 & 2 mutations

Breast and ovarian cancer occur more frequently in young women with BRCA 1 &2 mutations (respective cumulative risks from 37 to 85% and 10 to 20%), and raise specific gynaecologic problems as prophylactic surgery and hormonal treatments. Two medical files from 2 sisters with BRCA 1 mutation (exon 11) are presented and the authors discuss the therapeutic options chosen. BRCA 1 & 2 tumour suppressor genes seem to play a major role in the repair of cellular damages inducing by the estrogenic proliferative signal. The prophylactic mastectomy is effective for the breast cancer prevention but its acceptance is low. The oophorectomydecreases the ovarian risk (knowing the occurrence of peritoneal carcinomatosis in 1.8% of cases) and currently the breast cancer risk (RR = 0.47) by the hormonal privation: the hormone replacement therapy does not seem to increase the breast cancer risk in the small series published. The HRT is possible in women with BRCA mutation under medical supervision and if the doses of hormones are light. The first results concerning the chemoprevention by Tamoxifen are encouraging (RR = 0.38) in these patients, but more studies are needed. The oral contraception exerts an uncertain effect against ovarian cancer, but possibly enhances the breast cancer risk in this group of women (RR = 3.3).The management of women with BRCA mutation is varying according to their own priorities, which can change during their life.