The incidence of occult ovarian neoplasia and cancer in BRCA1/2 mutation carriers after the bilateral prophylactic salpingo-oophorectomy (PBSO): A single-center prospective study

Abstract

Background: Due to ineffective ovarian cancer (OC) screening programs, prophylactic bilateral salpingo-oophorectomy (PBSO) is suggested for BRCA1/2 genes mutation carriers. The reported incidence of clinically occult neoplasia and OC detected during PBSO varies widely (2-17 %), reflecting differences in studies design.

Objective: We aimed to prospectively evaluate the incidence of occult neoplasia in specimens collected during PBSO performed in a single tertiary center and to determine the effectiveness of this procedure in BRCA1/2 mutation carriers.

Study design: Between January 2010 and October 2016 a total of 564 new germline BRCA1/2 mutation positive women were identified and 71 carriers underwent laparoscopic PBSO. Patients were prospectively followed-up after the surgery and data on operation, age, complications, histological reports and BRCA1/2 gene mutation types were collected and analyzed.

Results: Serous tubal intraepithelial carcinoma (STIC) was diagnosed in 7 (9.85 %) and OC in 4 (5.6 %) women (one advanced (FIGO IIIC) and 3 early (FIGO IA/C) stages); total incidence 15.5 %. Women's mean age at the time of surgery was 46.5 years. The mean age of women diagnosed with STIC and OC was 45.9 years (42-64). The mean follow up time for women being diagnosed with OC/STIC was 3.72 years; no recurrence was observed. The median time to perform laparoscopic PBSO was 43 min. (ranging from 25 to 65 min.), no surgical complications occurred during this operation. Interestingly, we found statistically significant (P = 0.0105) enrichment of STIC lesions in BRCA1 c.4035delA (an established Baltic founder mutation) carriers group.

Conclusion: The incidence of pathological findings in BRCA1/2 mutation carries after PBSO is sufficiently high and our prospective study data supports PBSO as the most effective measure for reducing the risk of OC in BRCA1/2 mutation carriers. A novel finding of the enrichment of STIC lesions in BRCA1 c.4035delA carriers may show important biological differences in OC tumorigenesis between different BRCA1 mutations, which warrant further investigations.

Keywords: BRCA1; BRCA2; Ovarian cancer; Prophylactic salpingo-oophorectomy; Serous tubal intraepithelial carcinoma.