As Deborah Levenson writes in the May issue of Clinical Laboratory News, a public debate is taking place about whether all women should be screened for the tumor suppressor genes BRCA1 and BRCA2 (BRCA1/2).
Women with pathogenic BRCA1/2 mutations are 84% more likely to develop breast cancer and 39% more likely to develop ovarian cancer than women without the mutation. They also typically develop cancer at an earlier age. If women are aware of their BRCA1/2 status, however, they can make timely decisions about taking medications such as tamoxifen or undergoing prophylactic mastectomy or oophorectomy, all of which have been shown to reduce risk of cancer and overall mortality.
Thus, the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network recommend that women with a family history of breast, ovarian, and certain other cancers consider BRCA1/2 testing. Women diagnosed with breast cancer at especially early ages may also qualify for BRCA1/2 testing even without a suspicious family history.
In question, however, is whether all women should be screened for the genetic mutations.
Mary-Claire King, PhD, a professor of genomic sciences and medicine at the University of Washington in Seattle who first established the BRCA1/2–breast and ovarian cancer link, thinks they should. King, who won the prestigious Lasker Award for her groundbreaking research on BRCA mutations and cancer, outlined her position in an editorial published in the Journal of the American Medical Association.
Her recommendation is based on studies she and others have conducted that demonstrate that family history is not the best indicator of BRCA1/2 status. Widespread testing “enables mutation carriers to be identified independent of physician referral or family involvement,” King and her colleagues wrote.
Access and Cost-Effectiveness
Others in the field point to several barriers to implementing a population-based screening program in the United States. Researchers from UCLA, for instance, argue that routine testing is too costly and inefficient, given the low prevalence of pathogenic BRCA1/2 mutations here. Ashkenazi Jews have a higher prevalence of BRCA1/2—about 1 in 40—but BRCA1/2 prevalence in the general population is about 1 in 400. The UCLA authors reported in JAMA Oncology that population screening would prevent just 4 breast cancers and 2 ovarian cancers for every 10,000 women screened.
Although the cost of genetic screening has dropped in recent years and continues to decline, there are other costs associated with population screening, including genetic counseling and, if a mutation is discovered, medical care. There is also a shortage of geneticists and genetic counselors in many parts of the country.
“Medicine is all about targeting those at high risk in a way that gets the biggest bang for the buck,” said Steven Katz, MD, MPH, a professor of medicine, health management, and policy at the University of Michigan in Ann Arbor. Given the low prevalence of pathogenic BRCA1/2 mutations in American women, he said, population screening will not enhance life expectancy and quality of life for a large proportion of the population.
Pick up the May issue of CLN and learn more about the pros and cons of universal BRCA testing.