Long term follow up of BRCA1 and BRCA2 mutation carriers with unsuspected neoplasia identified at risk reducing salpingo-oophorectomy

Abstract

ObjectivesThe reported incidence of neoplasia identified at the time of risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA1/2 mutation carriers ranges from 4 to 12% but long-term outcomes have not been described. We evaluated recurrence and survival outcomes of mutation carriers with neoplastic lesions identified at RRSO. MethodsWe identified BRCA1/2 mutation carriers with neoplasia at RRSO at three institutions. Data was collected on clinical variables, adjuvant treatment and follow-up. ResultsWe identified 32 mutation carriers with invasive carcinomas (n=15) or high-grade intraepithelial neoplasia (n=17) that were not suspected prior to surgery. 26 occurred in BRCA1 and 6 in BRCA2 mutation carriers. Median and mean age for carcinomas were 50years and 49.3 respectively, significantly younger than for intraepithelial neoplasm, median 53years, and mean 55years (p=0.04). For the 15 invasive carcinomas, median follow up was 88months (range 45–172months), 7 recurred (47%), median time to recurrence was 32.5months and 3 have died of disease; 1 additional patient died of breast cancer. Overall survival was 73%, disease specific overall survival was 80% and disease free survival was 66%. For the 17 high-grade intraepithelial neoplasms, median follow up was 80months (range 40–150), 4 were treated with chemotherapy. One recurred at 43months and is currently not on therapy with a normal CA125, 16months later. All patients with noninvasive neoplasia are alive. ConclusionsBRCA1 and BRCA2 mutation carriers with unsuspected invasive carcinoma at RRSO have a relatively high rate of recurrence despite predominantly early stage, small volume disease. High-grade intraepithelial neoplasms rarely recur as carcinoma and may not require adjuvant chemotherapy.