The Journal of the American Medical Association published a study on Sept. 8, 2014 (doi:10.1001/jama.2014.12483), by Mary-Claire King, PhD, which recommends that all U.S. women over the age of 30 receive genetic testing for BRCA1 and BRCA2 mutations, whether or not they have a family history of breast or ovarian cancer.
Over the years, I have been extremely impressed by the dedication and amazing scientific contributions of Dr. Mary-Claire King to help identify and support individuals at risk for hereditary breast cancer. She is a well-respected researcher and her opinion is important to consider. However, as a genetic counselor who has worked with and advocated for families at risk for hereditary cancer risk for close to 20 years, I have concerns regarding her recent recommendation.
First, the data utilized to support this recommendation was generated on a very specific high-risk population, Ashkenazi Jewish men from Israel. In the Ashkenazi Jewish population, approximately 1 in 40 people carry a mutation in BRCA1 or BRCA2 versus 1 in 300 to 1 in 500 individuals from the general population. It is very difficult to take data from a high-risk population and apply it to the average person in a meaningful way.
In addition, three founder mutations in BRCA1 and BRCA2 account for close to 90 percent of the mutations identified in individuals who are of Ashkenazi Jewish descent versus thousands of other mutations that have been identified in other populations. In this population, testing is often done for just these three mutations rather than full evaluation of both genes by sequencing and large rearrangements (deletions or duplications of the gene).
This is a difference in cost from roughly $475 versus $2,000 to $4,000. Without a personal or family history suggestive of a potential inherited risk, the cost of the test would likely not be covered by most insurance companies as the average person would not meet current coverage criteria. These are very important factors impacting the ability to offer quality, easy-to-interpret testing in a cost-effective manner.
Many laboratories suggest a roughly four percent variant of uncertain significance rate on BRCA1/BRCA2 DNA testing. These are results where the meaning is unknown and the results should not be used in medical management decisions. However, it is a test result that is often misinterpreted and misunderstood, and has the potential to cause unnecessary anxiety and harm.
In Dr. King's commentary regarding the article, she suggests that laboratories report only clear normal or clearly harmful results and withhold variant results. The reason to withhold the variant results is to decrease confusion or misinterpretation of the results by patients or providers, but it also reveals a need for greater preparation and education of providers and the public before the value of general population screening could be fully realized. In addition, it emphasizes the importance of risk assessment and genetic counseling by an expert such as a genetic counselor.
I understand Dr. King's concept and her concerns that have led her to recommend universal screening, but the current system needs to do a better job at collecting sufficient family history information to accurately identify and triage patients who might benefit from genetic counseling and/or genetic testing. Without a systematic process to collect this information and without significant education for providers and the general public, many individuals may not have their mutation identified until after a cancer has occurred.
It is premature to suggest that the medical system is prepared to implement general population screening of BRCA1 and BRCA2 mutations, and more harm than good can happen as a result. A significant amount of work must be done to get the medical system and providers ready to handle the volume of patients, ensure that patients receive high-quality care and understand their results, ensure the psychosocial issues associated with genetic testing are addressed, and guarantee access to experts before making potentially life-changing medical decisions.
In addition, significant education is needed for the medical community and the lay public to fully realize the benefits of the technology to reduce cancer risks.
The data from Dr. King's study is important and I am grateful that she has initiated a conversation about how the population might maximize the benefit from genetic screening. It is imperative, however, that genetic counseling and risk assessment remain a part of the process for patients to make the best health choices for themselves.
It is premature to make this leap without putting the safeguards in place to protect the patients utilizing the DNA testing and resources to ensure the information is used well.