Authors' objectives:

The aim of this overview was to evaluate the analytical and clinical validity of BRCA1 and BRCA2 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 testing.

Authors' results and conclusions: The analytical performance of tests was evaluated from 27 unique studies. Sixty-eight reports with quality measures of psychosocial and ethical issues were identified and synthesized. Eighty-four reports that described the clinical outcomes in prophylactic or therapeutic studies were identified and synthesized to assess the benefit and harm of testing.

Authors' recommendations: The integration of BRCA1/2 testing into the health care system has occurred under a variety of conditions and at different rates of uptake. Variations exist in related services such as genetic counselling, and the regional availability of health care professionals and resources to deliver these services. There is no compelling evidence to suggest that one test performs better than another. Until better information becomes available, other factors such as test availability, ease of implementation, regulatory considerations, and price should be considered in deciding the method for testing. Although direct sequence analysis (DSA) is considered to be the gold standard, no two tests used the same index test and unit of analysis, thereby precluding comparisons. Clinically relevant mutations may be missed if DSA is used as a primary strategy for detecting BRCA1/2 mutations. Consequently, it was impossible to determine the most analytically valid molecular technique. Prophylactic surgery was associated with a reduced risk of breast and ovarian cancers in shortterm (<5 years) cohort studies, whereas surveillance strategies or hemoprophylaxis have not been shown to have a significant effect. Counselling is a critical component of the genetic testing process, informing the patient, and influencing perceived risk, anxiety, and uptake of testing. The public's knowledge of the association between cancer and genetics is limited. Ethical considerations include informed consent (or refusal), privacy, and confidentiality. Until better evidence becomes available, each jurisdiction will need to manage BRCA1/2 testing in accordance with their regulatory mechanisms, resources, and abilities. Policy and decision makers could conditionally reimburse BRCA1/2 testing for selected indications and restrict use to specific centres with identified protocols, or to particular health care providers to gather more information for future analysis.

Authors' methods: Systematic review

Project Status: Completed

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

Year Published: 2006

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: Canadian Agency for Drugs and Technologies in Health (CADTH)