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Non-BRCA carriers may opt to undergo interventions

Tuesday December 18, 2012
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Following BRCA testing, many women who are non-BRCA carriers undergo risk-reducing procedures and additional ovarian cancer screenings despite limited data to determine the effectiveness of these interventions among the general population, according to a study.

"The lifetime risk of developing ovarian cancer is only 1% to 2% in the general population; however, women with deleterious BRCA mutations have a cumulative lifetime risk of developing ovarian cancer of approximately 40% in BRCA1 carriers and approximately 20% in BRCA2 carries," according to background information for the study, which appeared Dec. 17 on the website of the Archives of Internal Medicine.

"In light of these statistics, there has been significant interest in defining the role of ovarian cancer screening in individuals who might be at higher-than-average risk."

Gabriel N. Mannis, MD, and colleagues with the University of California, San Francisco, surveyed 1,077 women after BRCA testing to identify the prevalence and post-test predictors of risk-reducing and screening interventions, including risk-reducing salpingo-oophorectomy (RRSO), screening transvaginal ultrasonography (TVUS) and screening serum cancer antigen 125 (CA-125).

BRCA test results were categorized as positive (shown to carry known deleterious BRCA mutation), true-negative (negative test result for a known deleterious family BRCA mutation), uninformative negative (negative BRCA results without a known family mutation), or variant of undetermined significance (found to have a change in DNA that has unknown effects on BRCA protein function).

Overall, 19.1% of eligible women underwent RRSO and 39.6% used screening procedures. Women who received a positive BRCA test result had increased odds of undergoing RRSO, TVUS and serum CA-125, while a true-negative BRCA result was associated with reduced odds for undergoing the three procedures.

Of the 71.8% of women who received uninformative results after BRCA testing, 12.3% underwent RRSO, 33.8% reported ever having undergone screening serum CA-125 since BRCA testing and 37.3% reported ever having undergone screening TVUS since BRCA testing.

Additionally, when the authors compared screening rates in the preceding three years on the basis of BRCA results, they found that about 69.6% of BRCA carriers, 30.2% of women with uninformative BRCA results and 9.6% of women with true-negative BRCA results reported having undergone ovarian cancer screening.

"Results of BRCA testing strongly predict RRSO and ovarian cancer screening," the authors concluded. Still, "use of RRSO and ovarian cancer screening was reported in a sizable percentage of non-BRCA carriers despite insufficient data to determine the effectiveness of these interventions."

In an accompanying commentary, Victor Grann, MD, MPH, and Maxine Ashby-Thompson, MPH, of Columbia University in New York City, wrote that the study "shows that genetic testing, even if negative, does not always allay deep-seated fears of cancer.

"Cancer biology is in the midst of a major transition that has led from a primary focus on oncogenes to a focus on systems. The challenge of the field is to identify persons needing additional or different treatment without scaring those who do not into additional interventions."

The study abstract is available at http://archinte.jamanetwork.com/article.aspx?articleid=1483958.


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