Government Panel Issues New Guidelines for BRCA1 and BRCA2 Testing

A. O. Berg et al. (U.S. Preventive Services Task Force), Annals of Internal Medicine, September 6, 2005

Is this for me? If your family history puts you at high risk for breast cancer, you might want to read this article.

Background and importance of the study:Abnormal BRCA1 and BRCA2 (BR stands for BReast, and CA stands for CAncer) genes account for about 5–10% of all breast cancers. An average woman (without an inherited abnormal breast cancer gene) in the United States has about a 12% risk of developing breast cancer over a 90-year life span. Women who have an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70.

Women with BRCA1 or BRCA2 abnormalities also are at increased risk of developing ovarian cancer. The lifetime risk for ovarian cancer is about 55% for women with BRCA1 mutations and about 25% for women with BRCA2 mutations. By comparison, about 1.8% of women without an inherited BRCA gene abnormality get ovarian cancer.

A genetic test can determine if a woman has an abnormal BRCA1 or BRCA2 gene. The test has been available for about 10 years, but it has some drawbacks:

• Normal test results don't guarantee healthy genes. In some families, many women have had breast cancer, yet they all test normal for the known breast cancer mutations. These families may have an inherited form of breast cancer caused by an abnormality or other gene that simply hasn't been identified yet.
• For some women, an abnormal test result can trigger anxiety, depression, or anger. Even though the result doesn't mean that a woman will definitely get breast cancer, many women with an abnormal gene assume they will.
• Genetic testing is expensive—it costs about $300 to $3,000 (depending on the extent of the testing). Many insurance plans cover the cost of the test for women at high risk. But the genetic counseling that is done before and after the testing is not routinely covered.

In the study reported here, a government panel reviewed the research on BRCA1 and BRCA2 genes and made recommendations about who should be counseled and tested for the breast cancer genes.

Study design: The U.S. Preventive Services Task Force is an independent, expert panel created by the government to evaluate things people can do to lower their risk of getting a disease or illness. The task force reviewed all the available research on BRCA1 and BRCA2 genes. Based on this research, the task force wrote guidelines on when women should have BRCA genetic counseling and testing. These are the first guidelines issued by the U.S. Preventive Services Task Force on any type of genetic testing.

Results: After reviewing all the studies on the BRCA1 and BRCA2 genes, the U.S. Preventive Services Task Force found no evidence that BRCA testing helps reduce a woman's risk of getting breast cancer or dying from breast cancer.

Only a small number of women who seek genetic testing will get a test result that says they have a breast cancer gene abnormality. About 2% of women with no significant family history of breast cancer, and less than 20% of women with a significant family history, will have positive test results. And only some of the women who find out they have a breast cancer gene abnormality decide to take some action to reduce their risk (for example, having risk-reducing surgery, which removes the breasts, ovaries, or both, or taking anti-estrogen drugs).

The task force also found that the results of genetic testing can be confusing and even misleading. For example, a woman with a strong family history of breast and ovarian cancer may get a test result that says, "no abnormality of BRCA 1 or BRCA 2 is present" (this is a "negative" test result). But this test result may be falsely reassuring. There may be another gene abnormality in her family that just hasn't been discovered yet. So a woman in this situation may still be at high risk for breast cancer (and ovarian cancer). She will still need to consider taking steps to reduce her risk, and she'll still need to be carefully monitored by her doctors.

Family history is a hugely important factor in determining who should receive genetic counseling. High-risk family history includes:

• more than one first-degree relative (mother, sister, or daughter) with breast or ovarian cancer,
• more than one second-degree relative (aunt, grandmother, or cousin) with breast or ovarian cancer,
• a diagnosis of breast or ovarian cancer in those relatives at a young age (50 or younger), and
• Ashkenazi (Eastern European) Jewish heritage.

Conclusions: The U.S. Preventive Services Task Force guidelines recommend the following:

• Genetic testing should be used very carefully.
• Doctors should carefully assess a woman's family history to determine if she could benefit from counseling and testing for the BRCA1 and BRCA2 genes.
• Women with a family history that puts them at high risk for breast cancer should be referred for genetic counseling to help them decide whether or not to have the test.
• Primary care doctors should collect the family history needed to decide if a woman should be referred for genetic counseling.

Take-home message: Genetic testing for BRCA1 and BRCA2 abnormalities has both benefits and drawbacks and isn't right for everyone. Many women affected by breast cancer—women with a family history of breast (and possibly ovarian) cancer—can benefit from genetic COUNSELING. Only some of these women will benefit from genetic TESTING. The U.S. Preventive Services Task Force wrote guidelines to help you and your doctor figure out who can benefit from genetic counseling and testing, and who is unlikely to be helped by all of this.

The task force guidelines say that your doctor should look at your family history and then refer you for genetic counseling if your history indicates that you might be at high risk for breast cancer.

The task force guidelines are similar to those recommended by other medical organizations, but are different in two ways:

• The guidelines emphasize referrals for genetic counseling before any testing is done.
• The guidelines recommend that primary care doctors collect the family history needed to decide if you should be recommended for genetic counseling.

Right now, most insurance companies don't routinely cover the cost of genetic counseling sessions. Because this government task force recommends counseling, insurance companies may change their policies. Also, most primary care doctors don't collect the type of family history information that's needed to decide if you're at high risk for breast cancer. These recommendations may change the type of information your doctor asks you to provide.

If you have a family history of breast or ovarian cancer and are concerned about your risk, talk to your doctor about genetic counseling and the pros and cons of genetic testing. If your primary care doctor or gynecologist isn't familiar with the information and test for BRCA1 and BRCA2, ask to be referred to a breast cancer genetics counselor.

A breast cancer genetics counselor can explain how the test works. If you decide to be tested, the counselor can use the results to estimate your risk more accurately. Once your risk is estimated, the counselor—together with your doctor—can develop effective strategies to reduce your risk of getting these cancers and a plan to follow you carefully over time so that any cancer that develops is detected as early as possible.