Heidi D. Nelson, MD, MPH; Miranda Pappas, MA; Bernadette Zakher, MBBS; Jennifer Priest Mitchell, BA; Leila Okinaka-Hu, MD; Rongwei Fu, PhD
Disclaimer: The findings and conclusions in this review are those of the authors, who are responsible for its content, and do not necessarily represent the views of the AHRQ. No statement in this review should be construed as an official position of the AHRQ or of the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Andrew Hamilton, MLS, MS, who conducted literature searches, and Amanda Brunton, BS, who provided assistance; both are affiliated with Oregon Health & Science University.
Financial Support: By the AHRQ under contract HHSA-290-2007-10057-1-EPC3.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1684.
Requests for Single Reprints: Heidi D. Nelson, MD, MPH, Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Mailcode BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098; e-mail, email@example.com.
Current Author Addresses: Drs. Nelson, Zakher, Okinaka-Hu, and Fu and Ms. Pappas and Ms. Mitchell: Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Mailcode BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098.
Author Contributions: Conception and design: H.D. Nelson, M. Pappas, B. Zakher.
Analysis and interpretation of the data: H.D. Nelson, M. Pappas, B. Zakher, J.P. Mitchell, L. Okinaka-Hu, R. Fu.
Drafting of the article: H.D. Nelson, M. Pappas, B. Zakher, J.P. Mitchell, L. Okinaka-Hu, R. Fu.
Critical revision of the article for important intellectual content: H.D. Nelson, M. Pappas, B. Zakher, L. Okinaka-Hu, R. Fu.
Final approval of the article: H.D. Nelson, M. Pappas, B. Zakher, R. Fu.
Provision of study materials or patients: H.D. Nelson.
Statistical expertise: H.D. Nelson, R. Fu.
Obtaining of funding: H.D. Nelson.
Administrative, technical, or logistic support: H.D. Nelson, M. Pappas, J.P. Mitchell.
Collection and assembly of data: H.D. Nelson, M. Pappas, B. Zakher, J.P. Mitchell.
Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2014;160:255-266. doi: 10.7326/M13-1684
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Published: Ann Intern Med. 2014;160(4):255-266.
Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.
To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.
MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.
English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality.
Individual investigators extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability by using established criteria.
Five referral models accurately estimated individual risk for BRCA mutations. Genetic counseling increased the accuracy of risk perception and decreases the intention for genetic testing among unlikely carriers and cancer-related worry, anxiety, and depression. No trials evaluated the effectiveness of intensive screening or risk-reducing medications in mutation carriers, although false-positive rates, unneeded imaging, and unneeded surgeries were higher with screening. Among high-risk women and mutation carriers, risk-reducing mastectomy decreased breast cancer by 85% to 100% and breast cancer mortality by 81% to 100% compared with women without surgery; risk-reducing salpingo-oophorectomy decreased breast cancer incidence by 37% to 100%, ovarian cancer by 69% to 100%, and all-cause mortality by 55% to 100%.
The analysis included only English-language articles; efficacy trials in mutation carriers were lacking.
Studies of risk assessment, genetic counseling, genetic testing, and interventions to reduce cancer and mortality indicate potential benefits and harms that vary according to risk.
Agency for Healthcare Research and Quality.
Analytic framework and key questions.
KQ = key question; MRI = magnetic resonance imaging.
* Clinically significant mutations of the BRCA1 or BRCA2 gene or related syndromes.
† Testing may be done on the unaffected woman, the relative with cancer, or the relative with the highest risk, as appropriate.
‡ No known mutation in relatives and none detected in the patient.
§ Known mutation in relatives but none detected in the patient.
|| Interventions include increased early detection through intensive screening (e.g., earlier and more frequent mammography and breast MRI), risk-reducing medications (tamoxifen and raloxifene), and risk-reducing surgery (mastectomy and salpingo-oophorectomy).
Summary of evidence search and selection.
* Identified from reference lists, hand-searching, suggestions from experts, and other methods.
† Results are provided in an additional publication (26).
‡ Studies that provided data and contributed to the body of evidence were considered to be “included.” Studies may contribute data to >1 key question. This number includes studies from the prior review as well as studies published since 2004.
Appendix Table 1. Models Estimating Individual Risk for BRCA Mutations to Guide Referrals
Appendix Table 2. Models Used as Reference Standards to Estimate Individual Risks for BRCA Mutations
Appendix Table 3. Studies of Genetic Counseling
Appendix Table 4. Studies of Distress After Genetic Testing
Table. Summary of Evidence
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Breast Cancer, Cancer Screening/Prevention, Hematology/Oncology, Prevention/Screening.
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