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].
A woman experiencing joint and mobility issues turned to holistic medicine after feeling that her regular doctors weren't adequately addressing her health problems. In recounting her health history to a new doctor, she also shared that she was concerned about her cancer risk since her deceased father had von Hippel-Lindau (VHL) syndrome and there was a strong history of breast cancer on her maternal side. VHL is a hereditary condition known to increase the risk of various tumors, including tumors in the blood vessels of the brain, spinal cord, and retina. Patients with VHL are also at higher risk for kidney cancer and pancreatic neuroendocrine tumors, as well adrenal gland tumors.
This doctor suggested the patient assess her genetic risk for cancer through the direct-to-consumer genetic testing firm 23andMe. The patient learned through this testing that she had several half-siblings. They talked about their test results and came to the conclusion that they were all conceived from the same sperm donor. The patient shared her suspicions with her mother, who denied this was the case. The mother further claimed the patient had been tested as a child for pathogenic variants in VHL but was negative; she did not provide any test records.
How was the case resolved?
The patient was confused and unsure what to believe. A few years ago, she sought out a genetic counselor on her own, hoping to further explore her genetic risks for cancer. The genetic counselor ordered a multi-gene panel that included analysis of VHL and breast cancer predisposition genes. Much to the patient's relief, the test turned out negative for cancer-linked pathogenic variants.
Based on her maternal family history of breast cancer, the patient met national guidelines for increased breast cancer screenings and began to receive it at a clinic for high-risk patients. The genetic counselor also provided psychosocial support to this patient about her 23andMe results. "We had a long conversation regarding … how she’s been coping with the possibility of non-paternity and the denial from her mother," the genetic counselor said. "We focused on her current support systems and navigating her feelings about the new information that came up from genetic testing.”
Why is this case concerning?
It is concerning that a physician recommended direct-to-consumer genetic testing for a patient that would not provide a full picture of her genetic risk for cancer, particularly given a known cancer predisposition syndrome in her father and her strong maternal family history of breast cancer.
"This genetic counselor had to be at a loss because 23andMe's testing wouldn't address VHL or comprehensively address the patient's family history of breast cancer," said Meagan Farmer, director of the cancer genetic counseling program at the University of Alabama at Birmingham and genetic clinical operations director at My Gene Counsel. "While DTC testing can, in some cases, provide medical insights, it couldn't address this patient's issues, and it opened a psychosocial Pandora's box."
The US Food and Drug Administration in 2018 allowed 23andMe to begin selling directly to consumers without a doctor's prescription genetic test reports for three BRCA1 and BRCA2 pathogenic variants most commonly found in people of Ashkenazi Jewish descent. But as part of that authorization, the agency cautioned that there are thousands of pathogenic variants in these two genes associated with increased risk of breast, ovarian, and other cancers, and that very few Americans carry these three specific risk variants. "The test … does not provide information on a person's overall risk of developing any type of cancer," the FDA said about the DTC test, adding that patients should consult a physician or a genetic counselor and conduct confirmatory testing before making decisions about treatment or surgery.
In 2019, 23andMe received FDA authorization for a test that detects the two most common variants associated with MUTYH-associated polyposis, which increases the risk of large precancerous polyps, and in turn, heightens the risk of colorectal cancer. The agency in this case noted similar caveats about the limitations of 23andMe's test and need for confirmatory testing.
The availability of these DTC test reports have raised concerns among medical geneticists and genetic counselors that patients may be harmed because they or their doctors won't understand the test limitations. These worries came to life in this patient's experience, though, fortunately, she sought out genetic counseling and was able to receive medical-grade testing and appropriate screening for being at increased risk for breast cancer.
On the other hand, the availability of DTC genetic testing does open up opportunities for patients, who otherwise wouldn't have gotten tested and learned they’re at risk. 23andMe has highlighted the stories of women who learned they had one of the three BRCA1/2 variants through its DTC service and learned not only that they had a greater predisposition for cancer but that they had Ashkenazi Jewish ancestry.
However, the variety of results offered by DTC testing services — from learning disease risks, to one’s traits like ear wax type, to discovering one's new relatives — has presented difficulties for this patient and many others, Farmer noted. Clearly, this patient did not expect to end up questioning who her biological father was when she agreed to genetic testing and was not prepared for unexpected or unwanted findings.
23andMe does provide pretest education to patients and has shown that its customers understand the limitations and risks associated with testing. Farmer has explored pretest education modules through different consumer genetic testing services, and with some, it’s possible to hurry through the pretest education. For a genetic counselor, this may not be an issue, "but if it's so easy to skip over it, then others can do it, too," she said, adding that pretest education, whether it’s reading some literature, watching a video, or speaking to a genetic counselor, often cannot fully prepare someone for what they might learn through genetic testing, "because you never expect it to happen to you."
Brianne Kirkpatrick, a genetic counselor and founder of Watershed DNA, a company that offers support to people who are struggling to understand unexpected genetic test results, is in favor of removing patients' access barriers to genetic testing but emphasized the need to help people once they get their results. "I've seen that people react to [genetic test] results in different ways, and not everybody needs the same amount of pretest or post-test support," she said. "Where I see the potential ... to help everybody across the board, whether they're doing a consumer test or a clinical test, is a triaging system set up after results come back and putting an emphasis on making sure people who get an unexpected result have a place to turn to next and understand that."
What could have been done differently?
In Farmer's view, given this patient's family history of breast cancer and a rare cancer-predisposing condition, her doctor should have referred her to a genetics specialist. Even if this doctor had a good reason to recommend DTC testing for this patient — for example, if she had Ashkenazi Jewish ancestry and wanted to find out if she harbored one of the three BRCA1/2 variants — Farmer stressed that she should still have received some guidance about the possibility of unexpected discoveries.
Given the pace at which the genetic testing industry is growing — 14 new genetic tests enter the market daily by one estimate — it is getting harder for doctors without genetics expertise to identify the right test for their patients. "Whose responsibility is it to make sure that patients are getting to the right test? Does it fall more on the provider to understand what they're talking about? Or does it fall on the companies offering testing?" said Kirkpatrick. "It's almost a sharing of responsibility that we haven't fully sorted out."
Representatives from genomics professional societies, National Institutes of Health divisions, and industry players are working together to develop guidelines for doctors, recognizing that the dearth of genetics specialists is putting pressure on primary care providers to manage patients who have had DTC genetic test results. The workgroup, called Inter-Society Coordinating Committee for Practitioner Education in Genomics/National Institutes of Health DTC-GT Project Group, recently released draft guidelines that recommend doctors conduct confirmatory, medical-grade testing to ensure the accuracy of DTC test results and outline what to do in different clinical scenarios.
It's critical, Farmer said, that doctors, at a minimum, understand the difference between DTC and medical-grade genetic testing. But if they're uncertain which test to order for a patient, physicians can always refer them to a medical geneticist or genetic counselor.