Occult ovarian cancers at the time of risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers

Abstract

1508 Background: Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in women with BRCA1 or BRCA2 (BRCA1/2) mutations. Occult ovarian cancers (OOC) detected at the time of RRSO have been reported, but there is wide variability in reported prevalence rates. Methods: We evaluated a prospective cohort of 647 women from 18 centers who underwent RRSO between 2001 and 2007 after a positive genetic test for disease-associated BRCA1/2 mutations. We estimated the prevalence of OOC. Results: Mean follow-up from genetic testing to RRSO was 1.01 years. OOC was detected in 16 of 647 women (2%). The mean age of women in whom OOC was detected was 51.7 versus 46.6 in women undergoing RRSO in whom OOC was not detected (p = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with a BRCA1 mutation. Two OOCs were detected on RRSO prior to age 40, both in BRCA1 mutation carriers. Thirty eight percent of women with OOC had stage I cancer, as opposed to 10% of women in the PROSE database diagnosed with ovarian cancer outside of screening (p = 0.006). Among the 283 women in whom pathology reports were available for central review, 71% of RRSO were performed at the respective PROSE sites (i.e. major genetic referral centers), while 29% of RRSO were performed at local sites (i.e. community hospitals). Ovarian and fallopian tube tissues removed at RRSO at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at nonreferral centers (76% vs. 24%, p < 0.001). Conclusions: RRSO reduces cancer risk and mortality in BRCA1/2 mutation carriers. Our results confirm that OOC is present at RRSO in BRCA1/2 mutation carriers, and suggest that OOC are more frequent after age 40 and are of a more favorable stage than cancers found outside the context of RRSO. Despite the fact that we examined surgeries after 2001, an unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO. Failure to perform adequate pathological examination may overlook OOC and have clinical consequences for women undergoing RRSO. No significant financial relationships to disclose.