Patients with double primary tumors in the breast and ovary - Clinical characteristics and BRCA1-2 mutations status

Objective. The aim of this study was to define the prevalence, clinical cha racteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC) p atients with a previous primary malignancy in the breast (PPMBr). Methods. The study population comprised 1240 consecutive Jewish Israeli wom en with pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and December 31, 1997. Demographic and clinical data were obtained fr om medical files and from a detailed questionnaire taken through a nationwi de epidemiological case-control study on OvC. Blood samples and tumor tissu es were collected for analysis of the three predominant germline BRCA1-2 Je wish founder mutations (185delAG, 5382insC, and 6174delT). Results. Fifty nine (4.7%) patients with OvC had a PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between the two diagnoses was 104 months (range 0-363 months). In the majority of the patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more than 1 y ear. The ovarian tumors were diagnosed in 47% of the cases following invest igation of patients' symptoms. In 41%, diagnosis was made as a consequence of check-up exams performed during the routine follow-up of BrC survivors. Patients with PPMBr were more likely to present with FIGO ovarian stage III -IV, compared to women with solitary OvC (73% vs 60.3%, P < 0.05), and less likely to have borderline tumors (3.4% vs 17.9%, P = 0.007). Family histor y of OvC/BrC was recorded in 26% of this group of patients compared to 10.5 % among patients with solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high prevalence of BRCA1-2 mutations (57%), irrespective of f amily history. Conclusions. Patients with PPMBr present with more advanced disease and inv asive-type epithelial ovarian tumors when compared to cases associated with solitary OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who h ad PPMBr is at least twice as high as in Jewish women with OvC as the solit ary disease. (C) 2000 Academic Press.