Hysterectomy as a risk-reducing procedure in BRCA1 and BRCA2 women.

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10611 Background: BRCA1/2 pathogenic variants (PV) are associated with an increased lifetime risk of developing several malignancies, particularly breast (BC) and ovarian (OC) cancers. The association between BRCA1/2 and endometrial cancer (EC) is controversial. Therefore, adding hysterectomy (HT) to risk-reducing (RR) bilateral salpingo-oophorectomy (BSO) is of uncertain benefit. In our multidisciplinary group this decision is personalized and takes in account other gynaecological pathologies or, for BC survivors, tamoxifen treatment. Objectives of this study are to assess the risk of EC on BRCA1/2 families registered in our program and to discuss the role of prophylactic HT in BRCA1/2 carriers. Methods: Pathologic confirmed EC cases were extracted from the prospective follow up cohort of 949 women diagnosed with a BRCA1/ 2 PV through the hereditary breast, ovarian and prostate program at our centre. Data was collected from the medical records. Results: Of the 949 women, 345 (36.3%) were diagnosed with a BRCA1 PV, 603 (63.5%) with a BRCA2 PV and 1 (0.1%) with PV in both genes. Of all women, 648 (68.3%) had a previous cancer diagnosis while 291 (30.7%) were in primary risk management. Excluding non-melanoma skin cancer, EC was the fourth most frequent neoplasia: BC (553, 85.3%), ovarian, fallopian and peritoneal cancer (117, 18.1%), thyroid cancer (15, 2.3%) and EC (8, 1.2%). BSO with HT was performed in 372 (39.1%) women: RR in 259 (69.6%; BRCA1 36.7%, BRCA2 63.3%, history of cancer 75.7%, no history of cancer 24.3%) and therapeutic in 113 (30.4%; ovarian/fallopian cancer 92.0%, uterine cancer 8.0%). BSO alone was performed in 174 (18.3%), being RR in 170 (97.7%; BRCA1 34.7%, BRCA2 65.3%, history of cancer 72.9%, no history of cancer 27.1%). HT alone was performed in 3 (benign disease). Regarding family phenotype, we found another 2 cases of EC in possible BRCA carriers. For these 10 cases of EC, median age of diagnosis was 58.5 years (42-75), 7 in BRCA1 and 3 in BRCA2 patients (pts). Pathology: endometrioid (5), serous (1), mixed (2, 1 endometrioid and serous and 1 endometrioid, squamous cell and seromucous) and carcinosarcoma (2). Six (out of 10) pts had previous BC: 4 BRCA1 (2 triple negative, 2 luminal-like) and 2 BRCA2 (2 luminal-like), 4 of them had previous tamoxifen use (2 BRCA1, 2 BRCA2). In 1 case the diagnosis of EC occurred after RR BSO ( BRCA1, no tamoxifen use) and another during the RR surgery ( BRCA2, tamoxifen use). There was no significant association of EC with BRCA1 or BRCA2 (two-sided p= 0.149). EC was the cause of dead in 5 pts (50%), all BRCA1. Conclusions: EC was the fourth most frequently cancer registered in our cohort of BRCA1/2 women. BRCA1 women, representing around 1/3 of all cohort, had 70% of all EC diagnoses. This apparent excess of BRCA1 EC diagnoses was not statistically significant. Tamoxifen may be a confounding factor. While an association was not confirmed at this time, our data also reinforces the need to discuss HT with our BRCA1/2 pts.

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