BRCA testing in women with familial, personal history of ovarian cancer may reduce cases in first-degree relatives

Testing all women with invasive nonmucinous epithelial ovarian cancer for BRCA mutations has as great a potential benefit for preventing ovarian and breast cancers in first degree relatives as 10 years of biennial mammography after age 50 in the general population, according to the results of an analysis published in The Journal of Clinical Oncology.

“Women with ovarian cancer represent a very important subpopulation in terms of BRCA testing because not only might they benefit from the testing, but their first-degree relatives have the opportunity to undergo testing and preventive measures that will substantially reduce their risk for breast and ovarian cancer,” said Janice S. Kwon, MD, from the division of gynecologic oncology, department of obstetrics and gynecology at the University of British Columbia, Vancouver.

“We tend not to think about mutation testing in women with ovarian cancer,” Kwon told HemOnc Today. “But any woman diagnosed with ovarian cancer should have a very careful family history obtained, and anyone that is eligible based on Society of Gynecologic Oncologists criteria should be advised about having BRCA mutation testing.”

Kwon and colleagues conducted a cost-effectiveness analysis of several different strategies of selecting women with ovarian cancer for BRCA mutation testing.

Although only 10% of all women with ovarian cancer have BRCA mutations, relatives who inherit these mutations have greatly increased risks of developing both breast and ovarian cancers.

For this reason Kwon and colleagues developed a Markov Monte Carlo simulation model to compare four criteria for BRCA testing in women with ovarian cancer:

No testing.
Only if Ashkenazi Jewish ancestry, personal history of breast cancer, or family history of breast/ovarian cancer according to SGO criteria.
Only if invasive serous cancer.
Any invasive nonmucinous epithelial cancer.

The researchers defined the net health benefit of testing as life expectancy for first-degree relatives; the primary outcome was the incremental cost-effectiveness ratio.

BRCA testing based on personal or family history and ancestry increased the average life expectancy of first-degree relatives by an average of 12 days when testing was based on SGO criteria. The cost of testing was $32,018 per life year gained compared with the reference strategy of no testing.

Testing of all women with serous cancers prolonged life of first-degree relatives by an additional four days but at a cost of $128,465 per life year gained compared with testing based on SGO criteria. Testing all cases of ovarian cancer extended life expectancy another three days at a cost of $148,363 per life year gained compared with testing only serous cancers.

The researchers then looked at how many cancers could be prevented in first-degree relatives based on testing strategy using the Markov Monte Carlo simulation model. Assuming about 14,000 women in the United States will be diagnosed with an invasive, nonmucinous epithelial ovarian cancer in the year 2009, about 10% or 1,400 women will have a BRCA mutation, according to the researchers. BRCA testing using SGO criteria — the most cost-effective method — could potentially reduce breast cancer cases in first-degree relatives by 14% and ovarian cancers cases by 39%.

“It is quite clear based on our experience at M.D. Anderson that there is a significant proportion of potentially eligible patients, ie, women with ovarian cancer, who are not undergoing testing,” Kwon said. “This will hopefully lead to increased awareness and an improved opportunity to open up BRCA testing to more women who have ovarian cancer.” – by Leah Lawrence

Kwon JS. J Clin Oncol. 2009;doi:10.1200/JCO.2008.21.4684.