%0 Journal Article
%T Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis.
%A Le Page C
%A Rahimi K
%A Rodrigues M
%A Heinzelmann-Schwarz V
%A Recio N
%A Tommasi S
%A Bataillon G
%A Portelance L
%A Golmard L
%A Meunier L
%A Tonin PN
%A Gotlieb W
%A Yasmeen A
%A Ray-Coquard I
%A Labidi-Galy SI
%A Provencher D
%A Mes-Masson AM
%J Gynecol Oncol
%V 156
%N 2
%D 02 2020
%M 31753525
%F 5.304
%R 10.1016/j.ygyno.2019.11.019
%X Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).<BR>We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.<BR>Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).<BR>Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.