Clinical and pathological features of ovarian cancer in women with germ- line mutations of BRCA1

Background: We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers. Methods: We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-line mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched for age and stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons 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 their parental relationships with documented mutant- gene carriers. Results: We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and I had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P