BRCA1/2 status and clinicopathologic characteristics of patients with double primary breast and ovarian cancer.

The aim of the study was to analyse the results of BRCA1/2 testing in a group of patients with double primary breast and ovarian cancer (DPBOC) in Slovenia. Additionally, the family history and the clinicopathologic characteristics of BRCA1/2 mutation positive and negative patients with DPBOC were analysed, comparing them to a group of untested patients with DPBOC. For these groups of patients, survival analysis was also performed. From the 52 patients who were invited to genetic counselling and testing, 20 responded positively (38% compliance). BRCA1/2 mutations were found in 60% (12/20): 45% BRCA1 and 15% BRCA2 (9 and 3 patients, respectively). There was significantly higher grade of ovarian cancer and significantly higher rate of multiple primary breast cancer in BRCA1/2 positive group. Additionaly, there was a trend towards higher rate of first-degree family history of breast cancer, a trend towards higher stage of ovarian cancer, and a trend towards breast cancer being the first cancer in BRCA1/2 positive group. According to survival analysis, the tested group was not a representative sample of the larger untested group (of 51 patients), so we estimate that the rate of BRCA1/2 mutations in DPBOC patients is probably less than 60%.

Risk factors and prognostic factors in patients with double primary cancer: epithelial ovarian cancer and breast cancer.

BACKGROUND AND OBJECTIVE: The most important known risk factor for ovarian cancer is the BRCA1-2 mutation, which is clinically often manifested through a positive family history of cancer of the breast and/or ovary. Whether other risk factors and prognostic factors in women with a positive family history of cancer of the breast and/or ovary and/or with BRCA1-2 mutation are important remains to be elucidated. Recent studies have shown that in the double primary breast and ovarian cancer (DPBOC), BRCA1-2 mutation is present in at least 86% of cases. Therefore, the group of patients with DPBOC, especially with epithelial ovarian cancer and breast cancer, is the most suitable for such an analysis. The aim of this study was to verify the hypothesis that, in this group, some other risk factors, in addition to a specific family history of cancer, as well as unfavourable pathomorphological prognostic factors, are more expressed than in a control group of patients with sporadic epithelial ovarian cancer only. METHODS: We compared the study group of 31 patients with DPBOC (epithelial ovarian cancer) to a control group of 62 patients with a single, sporadic epithelial ovarian cancer and negative specific family history. The data were obtained from the Cancer Registry of Slovenia and from clinical records. For every patient, we filled-in a protocol and analysed the data, comparing other risk factors in addition to specific family history and prognostic, clinical, and pathomorphological factors. Statistical analysis was performed using descriptive statistics, chi-square test and t-test. Multivariate analysis was also planned, but the necessary conditions were not met. RESULTS: In the study group, we found a higher percentage of positive non-specific family histories than in the control group, but the difference was not statistically significant. No difference in procreative risk factors was observed between the groups. There was a higher percentage of borderline significance of women from the study group that developed ovarian cancer between 45 and 59 years of age. In the study group, ovarian cancer was significantly more often found at Stage I, although the groups did not differ in detection procedures. Also, we did not find any differences in the distribution of tumour grades or histologic tumour types. CONCLUSION: The results did not confirm our hypothesis, yet they indicated some differences between the groups regarding the risk factors for ovarian cancer. Regarding the prognostic factors, we even found a significantly higher percentage of Stage I epithelial ovarian cancer in the study group, with no difference in the mode of detection. Considering the results that are not typical of BRCA-related cancer (what double primary cancer of the ovary and breast is supposed to be) and previous reports, we find it more likely that the patients with BRCA1-2 mutations represent only a subgroup within the group of patients with double primary breast and ovarian cancer.