CLINICAL AND PATHOLOGICAL FEATURES OF OVARIAN-CANCER IN WOMEN WITH GERM-LINE MUTATIONS OF BRCA1

Background We tested the hypothesis that ovarian cancers associated wi th germ-line mutations of BRCA1 have distinct clinical and pathologica l features as compared with sporadic ovarian cancers. Methods We revie wed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-fine mutations of BRCA1. Survival a mong patients with advanced-stage cancer and such mutations was compar ed with that in control patients matched for age and stage, grade, and histologic subtype of the tumors. A combination of single-strand conf ormation and sequencing analyses was used to examine the 22 coding exo ns and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of the ir parental relationships with documented mutant-gene carriers. Result s We identified 53 patients with germ-line mutations of BRCA1. The ave rage age at diagnosis was 48 years (range, 28 to 78). Histologic exami nation in 43 of the 53 patients showed serous adenocarcinoma. Thirty-s even tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, an d 3 were of low malignant potential. In 38 patients, the tumors were o f stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months fr om diagnosis, 20 patients had died of ovarian cancer, 27 had no eviden ce of the disease, 4 were alive with the disease, and 2 had died of ot her diseases. Actuarial median survival for the 43 patients with advan ced-stage disease was 77 months, as compared with 29 months for the ma tched controls (P<0.001). Conclusions As compared with sporadic ovaria n cancers, cancers associated with BRCA1 mutations appear to have a si gnificantly more favorable clinical course. (C)1996, Massachusetts Med ical Society.