CLINICAL-FEATURES OF OVARIAN-CANCER IN JAPANESE WOMEN WITH GERM-LINE MUTATIONS OF BPCA1

We analyzed the clinical features of 25 ovarian cancer patients who we re associated with germ-line mutations of BRCA1 from four site-specifi c ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years ). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients h ad stage I disease, 17 had stage III disease, and 3 had stage IV disea se. Thirteen patients with stage III disease who were treated with cis platin containing chemotherapy following tumor reduction surgery showe d more favorable outcomes in both the survival rate and disease-free i ntervals, compared with age-and treatment course-matched controls (5-y ear survival rate, 0.786 versus 0.303; median disease-free interval, 9 1.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test) . Our statistical model for the inheritance of susceptibility to ovari an cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations o f BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.