Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement: United States Preventive Services Task Force
United States Preventive Services Task Force
guidelines, u.s. preventive services task force
United States Preventive Services Task Force. Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement: United States Preventive Services Task Force. The Internet Journal of Oncology. 2004 Volume 3 Number 1.
Summary of Recommendations
The U.S. Preventive Services Task Force (USPSTF) recommends against routine referral for genetic counseling or routine
The USPSTF recommends that women whose family history is associated with an increased risk for deleterious mutations in
These recommendations apply to women who have not received a diagnosis of breast or ovarian cancer. They do not apply to women with a family history of breast or ovarian cancer that includes a relative with a
Although there currently are no standardized referral criteria, women with an increased- risk family history should be considered for genetic counseling to further evaluate their potential risks.
Certain specific family history patterns are associated with an increased risk for deleterious mutations in the
For women of Ashkenazi Jewish heritage, an increased risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer.
About 2% of adult women in the general population have an increased-risk family history as defined here. Women without one of these family history patterns have a low probability of having a deleterious mutation in
Computational tools are available to predict the risk for clinically important
Not all women with a potentially deleterious
Appropriate genetic counseling helps women make informed decisions, can improve their knowledge and perception of absolute risk for breast and ovarian cancer, and can often reduce anxiety. Genetic counseling includes elements of counseling; risk assessment; pedigree analysis; and, in some cases, recommendations for testing for
Among women with
Women with an increased risk family history are at risk not only for deleterious
The USPSTF has made recommendations on mammography screening for breast cancer, screening for ovarian cancer, and chemoprevention of breast cancer, which can be accessed at: http://www.preventiveservices.ahrq.gov.
Breast and ovarian cancer are associated with a family history of these conditions. Approximately 5% to 10% of women with breast cancer have a mother or sister with breast cancer, and up to 20% have a first-degree or a second-degree relative with breast cancer.1,2,3,4,5,6 Germline mutations in two genes,
Several characteristics are associated with an increased likelihood of
Penetrance is the probability of developing breast or ovarian cancer among women who have a
A systematic review of the evidence found no population-based randomized controlled trials of risk assessment and
Although several tools to predict risk for deleterious
The interventions that can be offered to a woman with a deleterious
Good evidence shows that MRI has higher sensitivity for detecting breast cancer among women with a
The evidence is also insufficient to determine the morbidity and mortality effects of intensive screening for ovarian cancer among women with
Good quality evidence from 4 randomized controlled trials shows that prophylactic tamoxifen reduces the risk for estrogen receptor-positive breast cancer in women without previous breast cancer.38, 39 A meta-analysis of these trials showed a relative risk for total breast cancer of 0.62 (95% CI, .46 to .83).1 Further analysis of the largest of these trials showed a possible reduction in breast cancer incidence for women with
Fair quality evidence is available on the effectiveness of prophylactic surgery to prevent breast and ovarian cancer. Cohort studies of prophylactic surgery have several methodologic limitations that should be considered when interpreting and generalizing their results, such as selection bias, retrospective study design, lack of a control group for estimation of benefit-attributable outcome in the untreated group, and inability to define risk reduction attributable to mastectomy in patients electing both mastectomy and oophorectomy.41 Four published studies (2 of fair quality, 2 that did not meet USPSTF quality criteria) of prophylactic bilateral mastectomy in high-risk women show a consistent 85% to 100% reduction in risk for breast cancer despite differences in study designs and comparison groups (for example, sisters42, matched controls43, a surveillance group44, and penetrance models45. Four studies of prophylactic oophorectomy reported reduced risks for ovarian and breast cancer46,47,48,49, although the number of cases was small and the confidence intervals for the only prospective study crossed 1.0 for both outcomes.50 Overall, oophorectomy reduced ovarian cancer risk by 85% to 100%, and reduced breast cancer risk by 53% to 68%.
No studies have described cancer incidence or mortality outcomes associated with genetic counseling, although 10 fair- to good-quality randomized controlled trials reported psychological and behavioral outcomes.1 These studies examined the impact of genetic counseling on worrying about breast cancer, anxiety, depression, perception of cancer risk, and intention to participate in genetic testing. Studies were conducted in highly selected samples of women and results may not be generalizable to a screening population. Five of 7 trials showed that breast cancer worry decreased after genetic counseling and 2 studies showed no significant effect.1 Three studies reported decreased anxiety after genetic counseling and 3 reported no significant effect. One study reported decreased depression after genetic counseling and 4 found no significant effect.1Results of a meta-analysis show that genetic counseling significantly decreased generalized anxiety, although the reduction in psychological distress was not significant.43 There is poor evidence (conflicting studies) regarding whether genetic counseling increases or decreases the accuracy of patients' risk perception.
The USPSTF examined the available evidence on harms of screening and intervention. Approximately 12% of high risk families without a
Population studies are needed to determine the prevalence and penetrance of various mutations in the
Enhanced screening with such methods as MRI needs to be better studied in high risk women. Future studies should examine the impact of intensive MRI screening on breast cancer mortality and on possible overtreatment. Studies specifically designed to examine the potential benefit of chemoprophylaxis in women with known deleterious
Recommendations of Other Groups
A few organizations have made recommendations on genetic susceptibility testing. Specific criteria for consideration of genetic evaluation, counseling, and mutation testing can be found in the references, below. The American College of Medical Genetics (ACMG) recommends risk assessment and genetic counseling prior to testing for
Members of the USPSTF
Corresponding Author: Ned Calonge, MD, MPH, Chair, U.S. Preventive Services Task Force, c/o Program Director, USPSTF, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, e-mail: firstname.lastname@example.org.
Members of the U.S. Preventive Services Task Force* are Alfred O. Berg, MD, MPH, Chair, USPSTF (Professor and Chair, Department of Family Medicine, University of Washington, Seattle, WA); Janet D. Allan, PhD, RN, CS, Vice-chair, USPSTF (Dean, School of Nursing, University of Maryland, Baltimore, Baltimore, MD); Ned Calonge, MD, MPH (Chief Medical Officer and State Epidemiologist, Colorado Department of Public Health and Environment, Denver, CO); Paul S. Frame, MD (Family Physician, Tri-County Family Medicine, Cohocton, NY, and Clinical Professor of Family Medicine, University of Rochester, Rochester, NY); Leon Gordis, MD, MPH, DrPH (Professor, Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kimberly D. Gregory, MD, MPH, (Director, Women's Health Service Research and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA); Russell Harris, MD, MPH (Professor of Medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); Mark S. Johnson, MD, MPH (Professor and Chair, Department of Family Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ); Jonathan D. Klein, MD, MPH (Associate Professor, Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY); Carol Loveland-Cherry, PhD, RN (Executive Associate Dean, Office of Academic Affairs, University of Michigan School of Nursing, Ann Arbor, MI); Virginia A. Moyer, MD, MPH (Professor, Department of Pediatrics, University of Texas Health Science Center, Houston, TX); Judith K. Ockene, PhD (Professor of Medicine and Chief of Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA); Diana B. Petitti, MD, MPH (Senior Scientific Advisor for Health Policy and Medicine, Kaiser Permanente Southern California, Pasadena, CA); Albert L. Siu, MD, MSPH (Professor and Chairman, Brookdale Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY); Steven M. Teutsch, MD, MPH (Executive Director, Outcomes Research and Management, Merck & Company, Inc., West Point, PA); and Barbara P. Yawn, MD, MSc (Director of Research, Olmstead Research Center, Rochester, MN).
*Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to http://www.ahrq.gov/clinic/uspstfab.htm.
Recommendations made by the USPSTF are independent of the U.S. Government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Individuals who wish to cite this recommendation should use the following format: U.S. Preventive Services Task Force. Genetic risk assessment and
Find more information about
Agency for Healthcare Research and Quality http://www.ahrq.gov/
U.S. Preventive Services Task Force Recommendations and ratings
The Task Force grades its recommendations according to one of 5 classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms):
U.S. Preventive Services Task Force Strength Of Overall Evidence
The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor):