This story does a nice job of describing a recent study that looked at the clinical validity of several cancer genetic test panels. The study looked at a group of women who were very high risk for breast cancer but tested negative for the BRCA1/2 genes and who were tested for other, potentially high-risk genes. It describes the potential harms associated with such test panels, touches on the authors’ reported conflicts of interest, and avoids disease mongering. It could have done better by specifying costs, interviewing independent experts, and by putting this evidence in context — explaining some general issues with genetic testing and their analytical as well as clinical validity.
About 5-10% of breast cancer cases in the US are linked to hereditary genetic mutations, the two best-known mutations being BRCA1 and BRCA2. Mutations in dozens of other genes have been studied and identified as possible risk factors for breast cancer.
Myriad Genetics owned a patent on these two tests until 2013, when the Supreme Court ruled that genes couldn’t be patented, thus invalidating their patents and their status as the only company that could offer BRCA1/2 genetic testing. Since this ruling, other companies have begun to offer multiple genetic test panels that are now marketed to doctors and to patients alike.
The main question behind these, and other (including non-cancer), genetic tests is what to do with the information generated by them. Are identified genetic mutations “clinically actionable”? Are the results meaningful enough to allow the medical team to alter or tailor clinical management? The availability of various panels of genetic tests, for cancer as well as for other diseases, has been controversial in the medical community.
At issue are the “analytical validity” of the test (Can the test accurately detect whether a specific genetic variant is present or absent?), as well as the “clinical validity” of the test (Can the test provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a patient or to a consumer?)
The article mentions that the tests themselves “are not more expensive than testing for the BRCA mutations alone,” but it doesn’t state what those BRCA-only panels cost. In addition, insurance coverage for panel testing is not as uniform as it is for BRCA 1/2 testing. There are established guidelines for BRCA 1/2 testing from the National Comprehensive Cancer Network that most insurance companies honor. There are not yet established guidelines for panel testing. We appreciate the nod to cost, but we thought a little bit more detail was needed here for a Satisfactory rating.
The story relays the benefits described in the study for the study population. It notes that 63 (about 4%) out of more than 1,000 women who test negative for BRCA mutations tested positive for non-BRCA mutations. “Of those, the researchers decided that 33 would have been considered for additional screening or prevention measures based on their results.” That description earns to the story a Satisfactory rating. Additional details on what screening and prevention measures might be recommended for which women — and some statement about whether those results are likely to apply to people outside of the study — would have been welcome.
Potential harms, including having uncertain results leading to psychological difficulties, were mentioned in a quote from the lead author, who also discussed the complexity of interpreting the results. The article also quoted him as saying that misinterpretation could potentially lead to “a drastic, unnecessary surgical procedure”.
The story describes the evidence as presented in the original article and includes some restraining comments from the researchers about the complexity of interpreting the tests and the fact that they are not advocating for broad-based testing. However, there are various major questions and issues related to genetic test panels themselves, including their “analytic validity” (the degree of accuracy with which a test detects the presence or absence of a mutation), and “clinical validity” (how well the mutation is related to the presence, absence, or risk of a specific disease), which are not mentioned. We would like to have seen those terms – key issues when reporting on the utility of genetic testing — mentioned and discussed somewhere in the article. (Or if not those specific terms then the issues that they are meant to describe.) This is important because this study looked at two specific panels, but gene mutations included in some other tests may have uncertain analytic/clinical validity. Related to these issues, the story doesn’t clarify that while the management of the women with positive “panel” test results might have changed because of the result, it’s not clear from this study whether their ultimate outcome (e.g. rate of cancer diagnoses or survival) was improved or to what extent because of the additional testing. Finally, it would have been great to see mention of the CDC’s ACCE model which is a “publicly-available analytical process for evaluating scientific data on emerging genetic tests”.
There was no disease mongering here. Breast cancer is a real concern to many women.
The article mentions that several of the study’s authors have links to the industry and to companies that produce the genetic test panels. The story also quotes from an editorial written by an expert who wasn’t involved with the study. Conducting an interview with an outside expert might have unearthed additional useful context, but the story is pretty solid here as it stands.
The piece in itself is about an investigation of the clinical usefulness of additional (alternative) genetic panels to the “routine” BRCA1/2 tests. So the story meets our standard here. But as mentioned before, there are serious concerns about the use and availability of genetic test panels and it would have been great to add some context.
Although availability isn’t explicitly addressed, the story does note that women and their physicians are “ordering a wide selection of multiplex tests daily,” from which one can infer that they are available. The story could have been more specific as to which panels were tested here and what others are available from physicians and even online. A good review is included in a table in this recent article from the NEJM.
The novelty of the research — the fact that there’s now some evidence that these tests may provide actionable information — is discussed. It would have been great to put this research and the tests themselves in context with recent legal and scientific advances in the field.
The story references an interview with the study’s lead author, so we can be sure it went beyond this news release issued about the study.