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Background Studies have suggested that the 5-year survival of women with ovarian cancer and a BRCA1 or BRCA2 mutation is better than expected. We sought to evaluate the impact of carrying a BRCA1 or BRCA2 mutation on long-term survival of women after a diagnosis of invasive ovarian cancer. Methods One thousand six hundred twenty-six unselected women diagnosed with invasive ovarian cancer in Ontario, Canada, or in Tampa, Florida, between 1995 and 2004 were followed for a mean of 6.9 years (range = 0.3 to 15.7 years). Mutation screening for BRCA1 and BRCA2 revealed mutations in 218 women (13.4%). Left-truncated survival analysis was conducted to estimate ovarian cancer–specific survival at various time points after diagnosis for women with and without mutations. Results In the 3-year period after diagnosis, the presence of a BRCA1 or BRCA2 mutation was associated with a better prognosis (adjusted hazard ratio = 0.68, 95% confidence interval [CI] = 0.48 to 0.98; P = .03), but at 10 years after diagnosis, the hazard ratio was 1.00 (95% CI = 0.83 to 1.22; P = .90). Among women with serous ovarian cancers, 27.4% of women who were BRCA1 mutation carriers, 27.7% of women who were BRCA2 carriers, and 27.1% of women who were noncarriers were alive at 12 years past diagnosis. Conclusion For women with invasive ovarian cancer, the short-term survival advantage of carrying a BRCA1 or BRCA2 mutation does not lead to a long-term survival benefit. [ABSTRACT FROM PUBLISHER]

Background: BRCA1 and BRCA2 mutations in general populations and in various types of cancers have not been well characterized. We investigated the presence of these mutations in unselected patients with newly diagnosed incident ovarian cancer in Ontario, Canada, with respect to cancers reported among their relatives. Methods: A population series of 1171 unselected patients with incident ovarian cancer diagnosed between January 1, 1995, and December 31, 1999, in Ontario, Canada, was screened for germline mutations throughout the BRCA1 and BRCA2 genes. Screening involved testing for common variants, then protein truncation testing of long exons, and then denaturing gradient gel electrophoresis or denaturing high-performance liquid chromatography for the remainder of BRCAI and BRCA2, respectively. Cox regression analysis was used to examine cancer outcomes reported by the case probands for their 8680 first-degree relatives. Population allele frequencies and relative risks (RRs) were derived from the regression results by an extension of Saunders-Begg methods. Age-specific Ontario cancer incidence rates were used to estimate cumulative incidence of cancer to age 80 years by mutation status. Results: Among 977 patients with invasive ovarian cancer, 75 had BRCA1 mutations and 54 had BRCA2 mutations, for a total mutation frequency of 13.2% (95% confidence interval ICI] = 11.2% to 15.5%). Higher risks for various cancer types in the general Ontario population were associated with BRCAI mutation carriage than with noncarriage, including ovarian (RR = 21, 95% CI = 12 to 36), female breast (RR = 11, 95% CI = 7.5 to 15), and testis (RR = 17, 95% CI = 1.3 to 230) cancers. Higher risks were also associated with BRCA2 mutation carriage than with noncarriage, particularly for ovarian (RR = 7.0, 95% CI = 3.1 to 16), female and male breast (RR = 4.6, 95% CI 2.7 to 7.8, and RR = 102, 95% CI = 9.9 to 1050, respectively), and pancreatic (RR = 6.6, 95% CI = 1.9 to 23) cancers. Cancer risks differed according to the mutation's position in the gene. Estimated cumulative incidence to age 80 years among women carrying BRCA1 mutations was 24% for ovarian cancer and 90% for breast cancer and among women carrying BRCA2 mutations was 8.4% for ovarian cancer and 41% for breast cancer. For the general Ontario population, estimated carrier frequencies of BRCAI and BRCA2 mutations, respectively, were 0.32% (95% CI = 0.23% to 0.45%) and 0.69% (95% CI = 0.43% to 1.10%). Conclusions: ERCA1 and BRCA2 mutations may be more frequent in general populations than previously thought and may be associated with various types of cancers. [ABSTRACT FROM AUTHOR]

Abstract: Background: The heritable fraction of ovarian cancer exceeds that of any other common adult cancer. Most inherited cases of ovarian cancer are due to a germline mutation in BRCA1 or BRCA2. It is important to have an accurate estimate of the proportion of ovarian cancer patients who carry a mutation and the specific factors which predict the presence of a mutation. Methods: We tested a population-based series of 1342 unselected patients diagnosed with invasive ovarian cancer between 1995–1999 and 2002–2004 in Ontario, Canada, for germline mutations in BRCA1 and BRCA2. The two genes were tested in their entirety, using a range of techniques, including multiplex ligation-dependent probe amplification (MLPA). Results: Among the 1342 women, 176 women carried a mutation (107 in BRCA1, 67 in BRCA2, and two in both genes) for a combined mutation frequency of 13.3%. Seven deletions were identified using MLPA (3.9% of all detected mutations). The prevalence of mutations was particularly high among women diagnosed in their forties (24.0%), in women with serous ovarian cancer (18.0%) and women of Italian (43.5%), Jewish (30.0%) or Indo-Pakistani origin (29.4%). A mutation was seen in 33.9% of women with a first-degree relative with breast or ovarian cancer and in 7.9% of women with no first-degree relative with breast or ovarian cancer. No mutation was seen in women with mucinous carcinoma. Conclusions: BRCA1 and BRCA2 mutations are common in women with invasive ovarian cancer. All women diagnosed with invasive non-mucinous ovarian cancer should be considered to be candidates for genetic testing. [Copyright &y& Elsevier]