September 29, 2005


In This Issue . . .

BRCA Screening: Increased Testing, Increased Harm?
Julie L McDowell

Inheriting mutations of the breast cancer susceptibility genes—BRCA1 and BRCA2—can push a woman’s lifetime risk of developing breast cancer up to 60–85%, as well as raise the risk for developing ovarian cancer to 26%. For those patients with a family history of these cancers, a genetic assessment might be recommended by clinicians so that interventions, such as surgically removing the breasts or ovaries, can be considered. But for patients without a family history, potential harms could outweigh any benefits, according to recommendations recently handed down by the U.S. Preventive Services Task Force (USPSTF), an independent panel of experts in primary care and prevention that evaluates and develops recommendations for clinical preventive services. This month, Strategies looks at the recommendations and some concerns about genetic testing as a preventative screening in the general population.

With the potential benefits of genetic testing now being touted to the public through the media and direct-to-consumer advertising, many women are requesting their primary care clinicians test them for inherited breast and ovarian cancer susceptibility, according to Heidi D. Nelson, MD, MPH, Professor in the Departments of Medical Informatics and Epidemiology and Medicine, Oregon Health & Science University (Portland), and principal investigator of the evidence review on genetic risk assessment and BRCA mutation testing in the Sept. 6, 2005, issue of Annals of Internal Medicine.

“The trend in this country has been for increased access to special testing,” said Nelson. “Genetic testing has probably captured the public’s interest because it is so new, and everyone’s heard of the Human Genome Project and remarkable technical breakthroughs and is very interested in how these technologies may apply to them.” This desire to learn one’s genetic status is strengthened when there is a test available for a disease like breast cancer, which has a high awareness factor. “Here we have a test that might actually make—in the public’s eye—things even better for prevention, and they are really interested in using it,” she added.

Slim Body of Evidence

Nelson and her colleagues’ evidence review formed the basis of the USPSTF’s recommendation against referring women for genetic counseling or testing for the breast cancer susceptibility genes—BRCA1 and BRCA2—when there is not a family history consistent with mutations in these genes. Researchers have found that BRCA mutations are clustered among certain ethnic groups—including Ashkenazi Jews, and those in the Netherlands, Iceland, and Sweden—as well as within specific families.

The trend towards increased public access to genetic testing has put primary care physicians in a tough position, because many of their female patients are asking them if they should get screened for BRCA mutations. But most primary care physicians don’t have sufficient training in the appropriate use and interpretation of genetic tests, and research on genetic screening in a primary care setting is lacking. Nelson and her colleagues found through their evidence review of BRCA testing studies from 1966–2004 that most available research focuses on women with pre-existing cancer and women referred to cancer centers, rather than women without cancer from the general population who would come to primary care clinics for screening. “Available research is helpful, but it does not apply to everyone,” explained Nelson

But just how good is the BRCA mutation testing in identifying cancer risk? Based on their statistical analysis of the body of evidence, Nelson and her colleagues found that unless a patient has a family history consistent with the mutation placing her in a high risk group, BRCA mutation testing probably wouldn’t provide benefits for a larger population. In addition, there are potential adverse effects once the result comes, such as the time, cost, and psychological stress associated with testing. If the result is indeterminate, this could heighten all three effects. If a patient doesn’t have the mutation, she might dismiss other preventive measures. “Do women whose tests are negative for deleterious mutations interpret that result to mean they are off the hook and don’t need to get any more mammograms?” asked Nelson. “In fact, most cancers occur in women without mutations. It doesn’t get you off the hook, it just puts you in another category. We don’t know how the results of these tests would really impact people’s lives.” Also, just because a patient tests positive for the mutation doesn’t mean she will definitely develop cancer. However, she might be encouraged to pursue surgical interventions such as removing her breasts or ovaries, even though she might never develop cancer.

So while research and technology developments are making these tests more broadly available to the general population, there is a large gap in the current evidence right now about the implications of genetic screening for the BRCA mutation. “At this point, because of the lack of information and potential harms, the Task Force decided to recommend against genetic screening for the general population,” said Nelson. “We need to conduct additional research to fully appreciate the implications of wide-spread testing. We prefer to think of the benefits of testing, but we need to realize that like with any test, it is imperfect and may also lead to potential harms. The benefits of the test may outweigh the harms in high risk women, and the challenge is to identify the most appropriate candidates for testing.”

For more information:
• This Annals of Internal Medicine article can be found online at
• Additional information on the USPSTF can be found at

Julie McDowell is the Editor of Strategies. She can be reached by email.

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