Women with Certain Type of Ovarian Cancer and BRCA Gene Mutation Have Improved Survival at 5 Years

Among women with invasive epithelial ovarian cancer, patients having a germline (gene change in a reproductive cell that could be passed to offspring) mutation in the BRCA1 or BRCA2 genes was associated with improved 5-year overall survival, with BRCA2 carriers having the best prognosis, according to a study in the January 25 issue of JAMA.

"Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 are the strongest known genetic risk factors for both breast and epithelial ovarian cancer (EOC) and are found in 6 percent to 15 percent of women with EOC," according to background information in the article. "The relative prognosis of BRCA1/2 carriers and noncarriers is unclear."

Kelly L. Bolton, Ph.D., of the National Cancer Institute, Bethesda, Md., and colleagues conducted a study to provide evidence of the relative effect of germline BRCA1 and BRCA2 mutations on prognosis for women with epithelial ovarian cancer. The study consisted of a pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1,213 EOC cases with pathogenic germline mutations in BRCA1 (n = 909) or BRCA2 (n = 304) and from 2,666 noncarriers recruited and followed up at variable times between 1987 and 2010. During the 5 years following EOC diagnosis, 1,766 deaths occurred.

The researchers found that 5-year overall survival was 36 percent for noncarriers of the gene mutations, 44 percent for BRCA1 carriers, and 52 percent for BRCA2 carriers. In a model only adjusted for study site and year of diagnosis, BRCA1 carriers had a more favorable survival than noncarriers, which improved slightly after additional adjustment for stage, grade, histology, and age at diagnosis. BRCA2 carriers had a greater survival advantage compared with noncarriers, particularly after adjusting for other prognostic factors.

The survival advantage for BRCA1 and BRCA2 carriers compared with noncarriers was present but less marked among women who reported a family history of ovarian, breast cancer, or both.

Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40–59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37–4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.