By Turna Ray

The US Preventative Services Task Force is seeking public comments on its systematic evidence review plan to assess under what conditions genetically testing asymptomatic women for their risk of developing hereditary breast and ovarian cancer has a positive impact on their health.

The USPSTF is in the process of updating its recommendation on BRCA mutation testing to gauge breast and ovarian cancer susceptibility. As part of that larger effort, it is calling for stakeholder input as it gathers evidence to answer specific questions on the risks and benefits of genetically testing asymptomatic women, who have a family history of breast and ovarian cancer but who themselves don't have these diseases.

The USPSTF's most recent recommendations on BRCA testing, issued in 2005, advise doctors against giving their patients routine referrals for genetic counseling or BRCA testing unless their family history suggests they might harbor mutations in tumor suppressor genes BRCA1 and BRCA2. The group recommends that if women have a family history that places them at increased risk for having these gene mutations, then doctors should refer them for genetic counseling and "evaluation for BRCA testing."

According to the National Cancer Institute, among Caucasian women in the US, between 5 percent and 10 percent of breast cancer patients and between 10 percent and 15 percent of ovarian cancer patients have BRCA1 and BRCA2 mutations. The risk of having these mutations is higher in women of Ashkenazi Jewish descent and those of Norwegian, Dutch, and Icelandic ethnicities. There is, however, limited data on how frequent these mutations occur among prevalent ethnic groups in the US, including African Americans, Hispanics, and Asian Americans.

"Although there currently are no standardized referral criteria, women with an increased-risk family history should be considered for genetic counseling to further evaluate their potential risks," the USPSTF notes in its 2005 recommendations. "Computational tools are available to predict the risk for clinically important BRCA mutations (that is, BRCA mutations associated with the presence of breast cancer, ovarian cancer, or both), but these tools have not been verified in the general population."

According to the USPSTF's proposal for comment, the group is seeking to gather evidence on whether BRCA testing reduces the incidence of breast and ovarian cancer, as well keeps women alive longer. Additionally, the USPSTF is seeking to gather data on how accurate physicians' risk assessment methods are for selecting which patients should receive BRCA mutation testing; what the benefits are of genetic counseling patients ahead of testing; and what the adverse effects of testing and counseling are.

USPSTF recommendations are carefully considered by private payors and factored into their coverage determinations for BRCA genetic testing. For example, Aetna in its clinical policy for BRCA testing cites the 2005 USPSTF recommendations to note that clinical models currently employed in medical practice for determining when women should receive genetic testing are based on women who already have cancer, and that the applicability of these models to screen asymptomatic or cancer-free women for BRCA testing is unknown.

"Available evidence suggests that current models for predicting BRCA mutation may tend to overestimate risk when family history is adequate and underestimate risk when family history is limited," Aetna states in the clinical policy. "Researchers have speculated that, in young women with limited family structures (i.e., fewer than two women who survived past age 45 in either parental lineage), the genetic models that are used to predict carrier status would underestimate the prevalence of BRCA mutations."

If USPSTF broadens its recommendations to include the asymptomatic population, it would certainly have a positive impact on Myriad Genetics' revenues for the BRACAnalysis test, the only commercially available genetic test that assesses BRCA mutations for hereditary breast and ovarian cancer susceptibility.

Read more:
USPSTF Updating BRCA Testing Recommendations for Asymptomatic Women; Accepting Public Input