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

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Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Evidence Synthesis Evidence Synthesis Number 37 Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Evidence Synthesis Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov 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, Oregon Investigators Heidi D. Nelson, MD, MPH Laurie Hoyt Huffman, MS Rongwei Fu, PhD Emily L. Harris, PhD, MPH Miranda Walker, BA Christina Bougatsos, BS September 2005 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. Preface The Agency for Healthcare Research and Quality (AHRQ) sponsors the development of Systematic Evidence Reviews (SERs) and Evidence Syntheses through its Evidence-based Practice Program. With guidance from the U.S. Preventive Services Task Force∗ (USPSTF) and input from Federal partners and primary care specialty societies, the Oregon Evidence-based Practice Center systematically reviews the evidence of the effectiveness of a wide range of clinical preventive services, including screening, counseling, and chemoprevention, in the primary care setting. The SERs and Evidence Syntheses—comprehensive reviews of the scientific evidence on the effectiveness of particular clinical preventive services—serve as the foundation for the recommendations of the USPSTF, which provide age- and risk-factor-specific recommendations for the delivery of these services in the primary care setting. Details of the process of identifying and evaluating relevant scientific evidence are described in the “Methods” section of each SER and Evidence Synthesis. The SERs and Evidence Syntheses document the evidence regarding the benefits, limitations, and cost-effectiveness of a broad range of clinical preventive services and will help further awareness, delivery, and coverage of preventive care as an integral part of quality primary health care. AHRQ also disseminates the SERs and Evidence Syntheses on the AHRQ Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and disseminates summaries of the evidence (summaries of the SERs and Evidence Syntheses) and recommendations of the USPSTF in print and on the Web. These are available through the AHRQ Web site and through the National Guideline Clearinghouse (http://www.ngc.gov). We welcome written comments on this Evidence Synthesis. Comments may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 540 Gaither Road, Suite 3000, Rockville, MD 20850, or e-mail [email protected]. Carolyn M. Clancy, M.D. Jean Slutsky, P. A., M.S.P.H. Director Director Agency for Healthcare Research and Quality Center for Outcomes and Evidence Agency for Healthcare Research and Quality ∗The USPSTF is an independent panel of experts in primary care and prevention first convened by the U.S. Public Health Service in 1984. The USPSTF systematically reviews the evidence on the effectiveness of providing clinical preventive services-- including screening, counseling, and chemoprevention--in the primary care setting. AHRQ convened the current USPSTF in November 1998 to update existing Task Force recommendations and to address new topics. iii Acknowledgments This Evidence Synthesis was funded by the U.S. Centers for Disease Control and Prevention (CDC) in partnership with the Agency for Healthcare Research and Quality (AHRQ) for the U.S. Preventive Services Task Force (USPSTF), and the investigators acknowledge the contributions of Ralph Coates, PhD, Liaison, CDC, and Gurvaneet Randhawa MD, MPH, Task Order and Medical Officer, AHRQ. Members of the USPSTF who served as leads for this project include Russell Harris, MD, MPH; Paul Frame, MD; Judith Ockene, PhD; Ned Calonge, MD, MPH; and Mark Johnson MD, MPH. The investigators thank Wylie Burke, MD, PhD, and Mark Helfand, MD, MS, for serving as consultants; expert reviewers listed in Appendix F of this report for commenting on draft versions; Andrew Hamilton, MLS, MS, for conducting the literature searches; and Peggy Nygren, MA, and Kim Villemyer for assisting with the manuscript. Request for Reprints Reprints are available from the AHRQ Web site at www.ahrq.gov (click on Preventive Services) and in print through the AHRQ Publications Clearinghouse (call1-800-358-9295). Disclaimer 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. Structured Abstract Context: 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. Objective: 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 papers 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
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