Precision Oncology News and My Gene Counsel have partnered to produce the "Genetic Testing Challenges in Oncology" series to highlight real-world issues that genetics experts and medical professionals are encountering as genetic tests are increasingly used in cancer care. Experts submit anonymized case reports to My Gene Counsel, and based on the details in these reports, Precision Oncology News writes a feature that describes the case history, challenges encountered by professionals in dealing with the case, and strategies they used in response to challenges or errors. The features also include a discussion with My Gene Counsel genetic counseling experts on better approaches that could be considered if similar cases are encountered in the future. In publishing this series, our aim is to educate experts in the field and foster discussion. If you would like to submit a case report, please email [email protected].
During a genetic counseling session with a 35-year-old woman and her mother, it came to light that the mother received genetic testing in a non-traditional setting. Neither the mother, nor the daughter had a personal history of cancer, but the mother's sister reportedly had a history of breast, ovarian, and colon cancers, as well as melanoma. They recounted that this relative was also a BRCA mutation carrier, though her test results were not available for review.
The mother told the genetic counselor that she had received pan-cancer multigene panel testing that was coordinated at a local home show, where a lab had a table set up. The test report came back positive for a pathogenic BRCA2 variant. The counselor reviewed the report carefully and noticed that while the top of the report bore the name of the entity that had collected the saliva sample from the mother, the fine print indicated that a different lab had done the testing. The testing lab, while relatively new and not a widely recognized name in genetic testing, was accredited by the College of American Pathologists and certified under federal lab standards, the Clinical Laboratory Improvement Amendments. Therefore, testing provided by this lab is considered medical grade.
Still, because the mother was tested in an atypical setting and the genetic counselor was not too familiar with the lab, she decided to order site-specific BRCA2 testing for the daughter through another, well-known, high-volume commercial lab, and also submitted another sample from the mother as a positive control. This was to ensure that the lab can detect the specific familial variant and determine if relatives are truly negative for that variant. However, this commercial lab was unable to detect the BRCA2 variant in the mother's sample, despite using next-generation and Sanger sequencing with multiple primers to make sure that the lab processes weren't missing anything.
When this lab informed the genetic counselor about the false positive, she reached out to another genetic counselor who had been recently hired by the original lab that tested the mother's sample collected at the home show. This counselor looked into the case and reported that the sample obtained at the home show was degraded and that a report should not have been issued in this case. The mother was upset after hearing this news, since she had started making plans for prophylactic mastectomy and oophorectomy, which would have been reasonable actions to take if the results had been accurate.
How was this case resolved?
The genetic counselor saw the daughter and mother back in the clinic and ordered pan-cancer multigene panel testing for the mother through the well-known commercial lab that was unable to find a BRCA2 mutation. This testing was also negative. However, the company that had collected the mother's sample at the home show had already billed her insurance company for that test, and now her insurer wouldn't pay for a second test.
However, the genetic counselor from the first lab who discovered that the sample had been degraded has reportedly been working on getting her employer to cover the cost of repeat testing, so the mother doesn't have to pay out of pocket. This counselor has also indicated that she is looking into the results of other people tested at the home show and checking for errors.
The mother was counseled that based on the negative results from repeat testing, she does not have a molecular diagnosis of BRCA-related breast and ovarian cancer syndrome. The genetic counselor, however, strongly urged the family to provide a copy of the aunt's BRCA mutation-positive result for review and explained the various possible interpretations if the report of a pathogenic BRCA variant in the family was mistaken. If the aunt’s results are obtained, the genetic counselor could then request the second commercial lab to review the family member's result and confirm that their test includes coverage that would have been able to detect the variant.
Why is this case concerning?
"Had it not been for her daughter wanting to get tested, the mother would have had prophylactic surgeries based on her [false-positive] test results from the home show," said Meagan Farmer, who is a certified genetic counselor and genetic counseling business manager at My Gene Counsel. That's concerning in itself, but it's even scarier, Farmer said, when one considers that this was a CLIA-certified and CAP-accredited lab that did the testing.
Many industry observers have said that given the growth in the genetic testing space, the current level of regulatory oversight for lab tests under CLIA and CAP may not be sufficient to protect the public health. For Farmer, this case illustrates why regulations need to be updated. "If I hand off a saliva sample to a reputable lab, I know they're going to test for sample integrity, have good quality assurance checks, and make sure that it is suitable for analysis. That's what was missing here," she said. "That sample was degraded, and it should have been caught and the results should not have been reported out."
Yet, this is a CLIA-certified lab. "At one time, if a lab had CLIA certification, we felt confident about the quality of the results, and now, that may not be enough," she said.
As the genetic testing industry grows and consumers become more interested in getting tested, new business models are emerging, where the entity collecting samples and interacting with consumers may not be the lab conducting the actual analysis. This multi-layered model lacks transparency, making it harder for consumers to evaluate for themselves the quality of the lab performing the testing. The companies involved in this case seem to have such a model where the lab doing testing was identified only in the fine print, Farmer said.
This case is also concerning in light of a recent public health alert from the US Department of Health and Human Services' Office of Inspector General about fraudulent genetic testing schemes. "Genetic testing fraud occurs when Medicare is billed for a test or screening that was not medically necessary and/or was not ordered by a Medicare beneficiary's treating physician," the OIG stated, describing scenarios where scammers are offering Medicare beneficiaries "free" screenings through telemarketing calls, at health fairs or booths at public events, and via door-to-door visits.
The OIG advised in the alert that individuals should have their own physician order testing after an evaluation and cautioned that if Medicare denies requests for a performed genetic test, they could be on the hook for paying for testing out of pocket, which can amount to thousands of dollars.
According to the genetic counselor in this case, when she reviewed the order form for the initial test the mother received, she noticed that under the section for a provider's name, just the name of the patient-facing commercial entity was provided and the private insurance company still paid for it. Medicare and private insurers in recent years have seen their spending on genetic testing increase, and as such, have become more vigilant about ensuring that testing is ordered by a physician for a covered indication. Farmer found it particularly worrisome that an insurance company wouldn't notice that a genetic test order form was missing a provider name. "I don't know how something like this would fall through the cracks," she said.
What could have been done differently?
When healthcare providers are reviewing a test result and see red flags — an unusual test setting, an unfamiliar lab, or results that are inconsistent with a patient's personal or family history of cancer — they should call the testing lab for additional information, Farmer said. "They may want to enlist a genetic counselor to review the results," she said, adding that repeat testing may be necessary. "Some commercial labs have pretty affordable self-pay options now, if insurance refuses to pay."
Additionally, for individuals interested in getting genetic testing, especially if they have a family history of cancer, Farmer advised speaking with a genetic counselor or a healthcare provider with specialized training to ensure that the right test is performed in a reputable lab. "There are so many labs and settings through which genetic tests are available now, and that's great from a patient access standpoint, but not all labs are created equal," she said. "It can be hard to spot a questionable lab."
Farmer also noted that healthcare providers shouldn't make medical decisions based only on a patient's claims about whether they have a particular mutation, and they should always try to get access to patients' or their relatives' genetic test reports and evaluate the results. In this case, this is why the genetic counselor asked the family to try to obtain the aunt's results. "If she is BRCA2 mutation positive and the mother came back negative, then she can feel confident that she is a true negative and not potentially at increased risk for BRCA-associated cancers," Farmer said, noting that there still are open questions for this family. "Without seeing that report, it's not certain if the aunt really had a BRCA mutation, a mutation in another gene, or had a variant of unknown significance but someone thought she was positive."