Genetic Risk Assessment and BRCA Mutation Testing

IN RESPONSE:

We appreciate Dr. Eisinger's and Dr. Horsman's concerns about the USPSTF recommendation for BRCA screening. First, they take issue with the Task Force's use of the term “increased risk” as a criterion for offering testing. This may have more to do with semantics than substance. Clinical criteria that suggest a woman is “at risk” for breast or ovarian cancer as defined by Drs. Eisinger and Horsman might mean she is “at increased risk” according to USPSTF nomenclature. The Task Force recommends that any woman “at increased risk” be referred for genetic risk assessment and possible testing. On the other hand, the USPSTF takes exception to the suggestion that all women with a family history of breast cancer, including those with a family history that is not suggestive of a BRCA mutation, be offered testing. Most breast cancer cases are unrelated to mutations in BRCA1 and BRCA2. The testing of women without a suggestive pedigree could result in a much broader use of screening in a population with a low prevalence of mutations. By the usual rules of medical testing, this would lead to a higher risk for false-positive test results and the attendant additional harms to health. We reiterate the USPSTF conclusion that the potential harms for women who are not at increased risk outweigh the benefits.

To the degree that USPSTF recommendations inform international decisions regarding preventive services, Drs. Eisinger and Horsman raise a clearly relevant point regarding the differences in insurance policy. The Task Force identified additional areas of social harms beyond those of insurability, including important issues in family dynamics and individual responses to information on personal susceptibility. Because the mission of the USPSTF is to provide recommendations for the delivery of preventive services in the United States, we believe these elements are critical to include. These were not, however, the predominant issues in weighing potential harms and benefits; instead, we focused on the harms of unnecessary treatment.

Finally, the USPSTF has no recommendation for or against the use of breast self-examination or clinical breast examination for breast cancer screening (a grade I recommendation on the basis of insufficient evidence). These services may or may not provide more benefit than harm, but the USPSTF concludes that the current body of evidence does not allow an evidence-based recommendation. There certainly may be cultural differences in the ways in which scientists in other settings judge the quality and certainty of research evidence. In applying the well-documented methods used by the USPSTF (1), however, the Task Force could not make recommendations for these services.