The U.S. Preventive Services Task Force (“USPSTF”) recently issued a report regarding the effectiveness of BRCA1/BRCA2 genetic tests for women and within the report, issued recommendations for preventive screening for women with and without confirmed familial history of breast, ovarian, tubal, or peritoneal cancer (“BRCA-related cancers”). Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement (“Report”). In addition to providing detailed, reasoned recommendations to the public, the Report reviewed the effectiveness of various interventions for women who are mutation carriers and identified research needs and gaps to improve clinical care.

BRCA Mutation Testing – 3 Prerequisites for Preventive Screening

The Report acknowledged that current genetic sequencing tests accurately detect BRCA mutations. However, the USPSTF recommended that genetic screening be performed only when: 1) an individual has personal or family history that suggests an inherited cancer susceptibility; 2) an individual has access to a health professional who is trained to provide genetic counseling and interpret test results; and 3) test results will aid in decision making. Initial testing of a family member who has breast or ovarian cancer is the preferred strategy in most cases, but the Report noted that it is nevertheless reasonable to test if no affective relative is available. The USPSTFR noted that is essential that before testing, the individual be fully informed about the implications of testing and has expressed a desire for it.

It is also recommended that individuals without linkages to families or groups with known mutations receive more comprehensive testing and if possible, testing should begin with a woman who has breast or ovarian cancer to determine whether affected family members have a clinically significant mutation.

The Report noted that while tests for BRCA mutations are highly sensitive and specific for known mutations, result interpretation is complex and generally requires post-test counseling. For example, the Report indicated that test results for genetic mutations are typically reported as one of: positive (potentially harmful mutation detected); variants of uncertain clinical significance; uninformative-negative; or true negative. It is noted that some studies suggested that an increased breast cancer risk is present in some women with true negative results. However, a comprehensive meta-analysis conducted for the USPSTF that included these studies found that breast cancer risk is generally not increased in women with true-negative results and that an uninformative-negative result occurs when a women’s test does not detect a potentially harmful mutation but no relatives have been tested or no mutations have been detected in tested relatives. It is reported that available tests may not be able to identify mutations in these families and that risk for breast cancer is increased in women with uninformative-negative results.

Interventions for Women Who Are BRCA Mutations Carriers

Interestingly, the Report indicated that evidence is lacking on the effect of intensive screening for BRCA-related cancer on clinical outcomes in women who are BRCA mutation carriers. For example, medications such as tamoxifen have been shown to reduce the incidence of invasive breast cancer in high-risk women in the general population, but they have not been studied specifically in women who are BRCA mutation carriers.

The Report indicated that cohort studies of risk-reducing surgery (e.g., mastectomy) substantially reduced risk for breast or ovarian cancer in high-risk women who are BRCA mutation carriers.

Research Needs and Gaps

In addition to a thorough review of the current research, assessment of treatment options and recommendation for genetic screening, the Report identified 5 areas for further research:

  1. Comparative effectiveness trials of approaches to risk screening and strategies to improve access to genetic counseling and BRCA testing for high-risk individuals are recommended;
  2. Studies to identify the most effective methods of delivery of genetic counseling, including access to genetic counseling in rural areas;
  3. Studies assessing the consequences of genetic testing for individuals and their relatives;
  4. The need for an expanded database or registry of patients receiving genetic counseling who were tested for BRCA mutations as well as additional information from women of varying socioeconomic, racial and ethnic groups; and
  5. Studies about the effectiveness of intensive cancer screening and risk-reducing medications and the effects of age at intervention on improving long-term outcomes are needed for women who are mutation carriers.

USPSTF Recommendations

In sum, the USPSTF Report recommended that women who have family members with BRCA-related cancers undergo screening with one of several screening tools designed to identify a family history that may be associated with an increased risk of BRCA-related mutations. Women receiving positive screening results should seek out and obtain genetic counseling and, if indicated after counseling, BRCA testing.

Genetic counseling or BRCA testing is not recommended for women whose family history is not associated with an increased risk for potentially harmful mutations in the BRCA1/2 genes.

Interesting, the Center for Medicare & Medicaid Services announced that it might reduce its reimbursement rate for the BRCA1/2 genetic test by about 50%. The CMS is inviting public on the reduced rate by January 27, 2014 to the website The CMS indicated that it would not consider any comments that are not sent to this email address.