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Cover of Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility

Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility

Evidence Syntheses, No. 37

Investigators: , MD, MPH, , MS, , PhD, , PhD, MPH, , BA, and , BS.

Oregon Evidence-based Practice Center, Portland, OR

Structured Abstract


Breast cancer is the second most common cancer in women in the U.S. and is the second leading cause of cancer death. Although less common, ovarian cancer is associated with high morbidity and mortality. Both breast and ovarian cancer are associated with a family history of these conditions and, in some families, the pattern of cancers suggests the presence of a dominantly inherited cancer susceptibility gene. Two genes, BRCA1 and BRCA2, have been identified as breast cancer susceptibility genes, and clinically significant mutations are estimated to occur in about 1 in 300 to 500 of the general population.


Screening for inherited breast and ovarian cancer susceptibility is a two-step process that includes an assessment of risk for clinically significant BRCA mutations followed by genetic testing of high-risk individuals. The evidence synthesis describes the strengths and limits of evidence about the effectiveness of selecting, testing, and managing patients in the course of screening in the primary care setting. Its objective is to determine the balance of benefits and adverse effects of screening based on available evidence. The target population includes adult women without preexisting breast or ovarian cancer presenting for routine care in the U.S.

Data Sources:

Relevant studies were identified from multiple searches of MEDLINE® (1966 to October 1, 2004), Cochrane Library databases, reference lists of pertinent studies, reviews, editorials, and websites, and by consulting experts.

Study Selection:

Investigators reviewed all abstracts identified by the searches and determined eligibility by applying inclusion and exclusion criteria specific to key questions about risk assessment, mutation testing, prevention interventions, and potential adverse effects including ethical, legal, and social implications (ELSI). Eligible studies had English-language abstracts, were applicable to U.S. clinical practice, and provided primary data relevant to key questions.

Data Extraction:

All eligible studies were reviewed and data were extracted from each study, entered into evidence tables, and summarized by descriptive and statistical methods as appropriate. Two reviewers independently rated the quality of studies using USPSTF criteria.

Data Synthesis:

A primary care approach to screening for BRCA genetic susceptibility for breast and ovarian cancer has not been tested. No studies directly evaluated whether screening by risk assessment and BRCA mutation testing leads to a reduction in the incidence of breast and ovarian cancer and cause-specific and/or all cause mortality. Assessment tools that estimate the risk of clinically significant BRCA mutations are available to clinicians, but have not been widely evaluated in primary care settings. Several referral guidelines have been developed for primary care, but there is no consensus or gold standard for use. Trials reported that genetic counseling may increase accuracy of risk perception, and decrease breast cancer worry and anxiety. Estimates of breast and ovarian cancer occurrence, based on studies of BRCA mutation prevalence and penetrance, can be stratified by family history risk groups that are applicable to screening. However, studies are heterogeneous and estimates based on them may not be reliable. Studies of potential adverse effects of risk assessment, genetic counseling, and testing reported decreased rather than increased distress. A meta-analysis of chemoprevention trials in women with unknown mutation status indicated statistically significant effects of selective estrogen receptor modulators in preventing breast cancer and estrogen receptor positive breast cancer, and significantly increased risks for thromboembolic events and endometrial cancer. Observational studies of prophylactic mastectomy and oophorectomy indicated reduced risks of breast and ovarian cancer in BRCA mutation carriers. Studies of patient satisfaction with surgery had mixed results; cancer distress improved, but self-esteem, body image, and other outcomes were adversely affected in some women. Applying this evidence to an outcomes table indicated that the numbers needed to screen to prevent one case of breast (4,000–13,000) or ovarian cancer (7,000) are high among women with an average risk of having a clinically significant BRCA mutation, and decrease as risk increases. Adverse effects also increase as more women are subjected to prevention therapies.


The evidence base for genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility as a screening strategy is limited by lack of studies demonstrating effectiveness, biases inherent in studies conducted in highly selected populations, and incomplete information on adverse effects.


Genetic risk assessment, genetic testing, BRCA1 and BRCA2 mutations, breast cancer, ovarian cancer.


Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0024, Task Order No. 2. Technical Support of the U.S. Preventive Services Task Force. Prepared by: Oregon Evidence-based Practice Center, Portland, OR.

This report may be used, in whole or in part, as the basis of the development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.

The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.


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Bookshelf ID: NBK43308PMID: 20722133


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