title: Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers.
abstract: Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in BRCA1 or BRCA2 (BRCA1/2) mutation carriers. Occult ovarian/fallopian tube cancers (OOC) detected at the time of RRSO have been reported in several studies with wide variability in reported prevalence. We estimated the prevalence of OOC in a prospective cohort of 647 BRCA1/2 mutation carriers from 18 centers (PROSE consortium) who underwent RRSO between 2001 and 2008. OOC was detected in 16 of 647 women (2.5%). The mean age at RRSO was 51.7 in those with OOC versus 46.6 in those without OOC (P = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with BRCA1 mutations. Thirty-eight percent of women with OOC had stage 1 cancer versus none of the women in the PROSE database diagnosed with ovarian cancer outside of screening. Among 385 women (60%) in whom pathology reports were available for central review, 246 (64%) RRSOs were performed at participating PROSE centers while 139 (36%) were performed at local sites. Ovarian and fallopian tube tissues removed at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at non-referral centers (75% vs. 30%, P < 0.001). Our results confirm that OOC may be found at the time of RRSO in BRCA1/2 mutation carriers and suggest that OOC are of a more favorable stage than cancers found outside RRSO. An unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO.
authors.affiliation: Abramson Cancer Center, The University of Pennsylvania School of Medicine, 3W Perelman Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA. Susan.domchek@uphs.upenn.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.forename: Ellen
authors.initials: E
authors.lastname: Matloff
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Wendy
authors.initials: W
authors.lastname: Rubinstein
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Stephen
authors.initials: S
authors.lastname: Rubin
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weitzel
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pichert
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Gail
authors.initials: G
authors.lastname: Tomlinson
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Fergus
authors.initials: F
authors.lastname: Couch
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D005060:Europe; D005185:Fallopian Tube Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009656:North America; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D015995:Prevalence; D011322:Primary Prevention / Q000379:methods*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human