Authors' objectives: The aim of this report was to evaluate the analytical and clinical validity of BRCA1/2 genetic testing; to assess the contribution of molecular testing to genetic counselling and clinical management; and to discuss the ethical and psychosocial issues inherent in BRCA1/2 testing.

Authors' results and conclusions: The analytical performance of BRCA1/2 mutation testing, primarily in high risk families and founder populations, was examined. For studies of analytical validity of BRCA1/2 testing, information on each method was extracted, and calculations of sensitivity and specificity were reported. High variability was found between studies. Although most studies used direct sequence analysis (DSA) as a gold standard, no two tests used the same index test, thereby precluding comparisons of methods. Clinically relevant mutations may be missed if DSA is used as a primary strategy for detecting BRCA1/2 mutations. As a result, the most analytically valid molecular technique for BRCA1/2 testing could not be determined. The contribution of BRCA1/2 testing to the clinical management of unaffected carriers and affected carriers was examined. Data regarding the influence of testing on clinical management was limited, partly because of the limited treatment options available. Prophylactic surgery was shown to reduce the risk of breast and ovarian cancers in cohort studies, whereas surveillance strategies or chemoprophylaxis have not been shown to offer significant effects for cancer risk.

Authors' recommendations: BRCA1/2 genetic testing is an emerging practice. The decision to offer BRCA1/2 testing is based on short-term cohort studies that suggest prophylactic surgery reduces the risk of breast and ovarian cancers for mutation carriers. There is insufficient evidence to suggest that a positive BRCA1/2 test result will lead to clinical management decisions that reduce long-term mortality and morbidity. Among the options that could be considered by policy and decision makers are conditional reimbursement of BRCA1/2 genetic testing for selected indications, and restricted use to specific centres with identified protocols or to particular health care providers while more information is gathered. In the literature identified for this report, there was insufficient evidence to conclude that a particular molecular technique demonstrated overall superior analytical performance compared with another molecular technique. Other factors should be considered in selecting the method used for testing. Future research should seek to overcome the methodological limitations identified in the studies selected for this report, so that quantitative analyses can be conducted and clear comparisons can be made. This applies not only to fundamental research, but also to the monitoring of clinical and technical practices, and to the follow-up of families undergoing genetic counselling and testing to measure outcomes. Scientific data are accumulating rapidly. If the expansion of testing or consensus guidelines are pursued in the future, an update of this report should be considered.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.cadth.ca/

Year Published: 2006

URL for published report: https://www.cadth.ca/sites/default/files/pdf/175_brca_tr_e.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Agency for Drugs and Technologies in Health

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553; Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: <p>Canadian Agency for Drugs and Technologies in Health (CADTH)</p>