Women with a high risk of breast cancer or ovarian cancer may benefit substantially from genetic counseling and testing for BRCA-1 and BRCA-2 gene mutations, but other women—about 98% of women in the U.S.—should not be routinely offered these services, advises the U.S. Preventive Services Task Force. On September 6, 2005, the task force published its latest evaluation of evidence regarding the value of genetic counseling and testing for these markers of susceptibility to breast and ovarian cancer. The task force is recommending that only women at high risk for these mutations be routinely referred for genetic counseling and evaluation for this genetic test; for other women, the task force warns that the potential harms of testing and subsequent medical interventions outweigh the benefits of routine referral and testing.

Below is a summary of the recommendation made by the task force for each risk group.

Genetic counseling and evaluation for BRCA gene mutations are not routinely recommended for women who do not have a family history that suggests they are at risk.

Only about 2% of adult women in the general population have a family history that identifies them as at increased risk, says the task force. A woman who undergoes this testing even though she has a low risk for breast and ovarian cancer will most likely derive little or no benefit but opens the door to potential harms, concludes the task force. The testing itself exposes the woman, and her relatives, to a quagmire of ethical, legal, psychological, financial, and social harms, even though her body may never develop the disease. The problem is that medical interventions that may be suggested after a positive test result have known harms; for a woman with low risk, potential harm from interventions can be a greater threat than the risk of disease.

Interventions may include intensive screening of the ovaries and breasts by a variety of methods (increasing the risk for overdiagnosis and overtreatment), invasive surgeries (removal of the breast and/or ovaries—each with their own risks and possible complications), and toxic cancer drug regimens (with harmful side effects). In addition to the physical risks and difficulties, testing and intervention can be psychologically and financially difficult and damaging.

Genetic counseling and evaluation for testing are recommended for women at high risk for harmful BRCA mutations.

A woman’s family history of breast and ovarian cancer, both on her father’s and mother’s side, should guide physicians in recommending counseling or testing, says the task force, which outlined specific criteria. Women with certain specific family history patterns have an increased risk for developing breast or ovarian cancers associated with two specific gene mutations, known as BRCA-1 and BRCA-2. Not all women with a family history of breast or ovarian cancer have these mutations, however.

For non-Ashkenazi Jewish women, these situations are of concern:

Breast cancer in family: Bilateral (both breasts) breast cancer in a first-degree relative (mother, sister, daughter); breast cancer in 2 first-degree relatives—1 of whom was diagnosed by age 50 or younger; breast cancer in 3 first- or second-degree (aunt, cousin) relatives; or breast cancer in a male relative

Ovarian cancer in family: Ovarian cancer in 2 or more first- or second-degree relatives

Breast and ovarian cancer in family: Breast and ovarian cancer among first- and second-degree relatives or both breast and ovarian cancer in a first- or second-degree relative

For women of Ashkenazi Jewish descent, for whom the threat is greater, the criteria are broader:

Breast or ovarian cancer in family: any first-degree relative or 2 second-degree relatives on the same side of the family

The task force also recommends referral for genetic counseling in this situation:

Breast or ovarian cancer and known BRCA mutation in family: Breast or ovarian cancer diagnosed in the family and a relative is known to have a harmful BRCA-1 or BRCA-2 mutation

Genetic counseling can help women at risk make informed decisions about testing and the prevention strategies they wish to pursue. The potential benefits from discussion of testing and from medical interventions may be substantial for these women, concludes the task force. There is evidence, for example, that women with the mutated genes who have preventive surgery have a significantly decreased incidence of breast and ovarian cancer.

Despite the limits of current knowledge, the task force finds that genetic counseling and the BRCA blood test may be of substantial benefit for women in the high-risk group. For women without a family history, routine referral and susceptibility testing are not advised because the potential harms appear more compelling than the benefits.

The task force statement, published in the September 5 issue of the Annals of Internal Medicine, summarizes differences in the recommendations of other groups. The journal also contains a concise summary for patients (see link below). The summary helps women recognize high-risk genetic situations.

Sources

S1
U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: U.S. Preventive Services Task Force recommendations (clinical guidelines). Ann Intern Med. 6 Sept 2005;143:355-61.

S2
U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: U.S. Preventive Services Task Force recommendations (summaries for patients). Ann Intern Med. 6 Sep 2005;143:I-47. Available on the Internet at http://www.annals.org/cgi/content/full/143/5/I-47. Accessed 24 Oct 2005.