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, the 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 24-year-old woman came to see a genetic counselor to discuss her inherited risk for breast cancer. She claimed she had undergone genetic testing at age 16 due to a strong history of breast cancers on her mother's side of the family and had a pathogenic variant in either the BRCA1 or BRCA2 gene; she couldn't remember which. The patient could not find a copy of the test report from eight years earlier. She further told the genetic counselor she had recently gone to see her physician because she had worrying symptoms of breast cancer — nipple discharge and persistent pain in one breast and redness and warmth in the other. The mammogram turned out normal, but based on her reported genetic and familial cancer risk the doctor was considering bilateral mastectomy and bilateral salpingo-oophorectomy in the future.
Curiously, the patient told the genetic counselor that her mother and her maternal aunt, who both had breast cancer at a young age, had tested negative for the familial pathogenic variant. The genetic counselor and patient made further attempts to locate the genetic test report from her physicians without success. The genetic counselor recommended the woman get tested again using a multi-gene panel, since she wouldn't be able to counsel the patient appropriately without knowing the specific cancer risk variant she had.
When the results came back, it turned out this patient did not have pathogenic variants in BRCA1/2, known to increase the risk of breast, ovarian, pancreatic, and other cancers. She did have a pathogenic variant in a different gene, CHEK2, associated with increased risk for breast, colorectal, and other cancers. The National Comprehensive Cancer Network recommends patients with pathogenic variants in BRCA1/2 consider risk-reducing mastectomy, as well as oophorectomy by a certain age. When it comes to CHEK2 pathogenic variants, however, the guidelines body says there is insufficient evidence to recommend breast removal based on a positive result alone, and importantly does not recommend oophorectomy.
How was this case resolved?
When the genetic counselor told the patient about the latest genetic test results, she was very confused. While the new test was being done, the young woman had continued to search for her old report, and she had finally managed to get a copy from her mother. According to the patient, the report said she had a BRCA2 pathogenic variant. The genetic counselor asked to see the report so she could call the testing lab for more information.
Upon receiving the report, the genetic counselor noticed it appeared to be from a reputable lab she was familiar with, but it had some irregularities. There were typos, the formatting differed in places, and the phone number listed for the physician was disconnected. Moreover, the accession number the lab uses to track each test within its system was falsified, not in the correct format, and didn't match to any patient in the lab's database. After further consultation and review, the lab told the genetic counselor that this report was falsified and forged by an outside source.
This raised a lot of questions for the genetic counselor. She discussed the case with her genetic counseling colleagues to explore possible explanations for the falsified report. Could the patient's mother have falsified the report to ensure that her daughter would receive increased screening? According to this young woman, by age 23, she had received two mammograms and three breast ultrasounds. (The patient was uninsured when she saw the genetic counselor and her prior physicians were in Mexico, so the genetic counselor wasn't able to obtain medical records to confirm her screening history.)
Munchausen syndrome by proxy — when someone tries to garner sympathy by falsely claiming to have an illness — could also be at play here, the genetic counselor thought. Sometimes, when there is a cancer risk variant in the family, it is easy to cast blame. One possibility the genetic counselor considered is that whoever falsified the report may have wanted to blame the father's side of the family, since the patient said that her mother and aunt were negative for this variant.
The genetic counselor told the patient that she did not have the BRCA2 variant in that original report, and that she should no longer share it with medical providers. Although, according to the patient, she had gotten this forged report from her mother, the genetic counselor didn't want to probe further about how the information may have been falsified. Instead, the genetic counselor focused on the fact that according to this patient's actual genetic test results, she had been receiving the incorrect management recommendations based on the assumption that she was "BRCA positive" and that her management should be based on the CHEK2 pathogenic variant she did have. The genetic counselor also recommended genetic testing for the patient's mother and father since she could have inherited the CHEK2 pathogenic variant from either side and both parents had a personal history of cancer — the mother had breast cancer at age 34 and the father had colon cancer at age 46.
Upon receiving the news, the patient seemed "somewhat anxious," according to the genetic counselor, but not as much as she would have expected. The patient said this didn't change much in terms of her understanding of her own cancer risk. Even if she didn't have the BRCA2 variant, the young woman still considered herself to be at high risk for breast cancer based on family history and was still considering prophylactic mastectomy. She was no longer considering oophorectomy, however.
The genetic counselor recognized that this was a young woman with concerning breast symptoms, who currently lacked insurance coverage and had a strong family history of early-onset breast cancer. It may very well be that these other issues are at the forefront of her mind, and she may need more time to process the news of the falsified report, the genetic counselor said. She has tried to follow up with the patient about her parents' testing, but the patient hasn't returned her calls.
Why is this case concerning?
The genetic counselor in this case was very concerned that this patient had been receiving inappropriate management based on a falsified report and that this had gone unnoticed for eight years. The forged report also delayed the opportunity for the patients' family members to receive appropriate screening and management.
Although in this case, the genetic counselor was able to spot the irregularities in the falsified report, a doctor reviewing the information quickly may have missed them. "What scares me is imagining a busy physician taking a quick glance at a report made to look like it is from a reputable lab, seeing a BRCA2 positive result, and moving forward with risk-reducing surgeries," said Meagan Farmer, a genetic counselor and genetic clinical operations director at My Gene Counsel.
It is not uncommon for genetic counselors to hear patients say they are "BRCA positive," but once they actually see the report, it'll turn out to be something different — a variant of unknown significance (VUS), or a pathogenic variant in a different gene, or a negative result — with entirely different clinical implications. In such cases, Farmer said, once patients become attached to a certain explanation for their cancer risk, it can be very unsettling for them to give up that narrative, even in the face of new information.
This is the first case Farmer has heard of where a falsified report was the source of the misunderstanding. Even with the knowledge of a falsified report and after learning that she had a pathogenic variant in a different gene with different management implications, this woman's view of her own cancer risk didn’t shift much. "She thought she was high risk before based on a certain genetic explanation, and she understands she is high risk now," Farmer said.
What could have been done differently?
This is an unusual case with a lot of unanswered questions. This patient claimed to have gotten genetic testing as a minor, at 16 years old, and the circumstances surrounding the testing are unclear. Genetics experts are cautious when it comes to testing minors for adult-onset conditions. Such testing should only be done, according to Farmer, after carefully factoring in the family's cancer history and providing pretest genetic counseling to ensure that the patient understands the risks and benefits, as well as the option to delay testing until adulthood.
The genetic counselor in this case did the detective work necessary to identify the red flags in the patient's story. Even though the patient said she was "BRCA positive," the genetic counselor found it odd that the patient's mother and maternal aunt, who had breast cancer at a young age, were "BRCA negative." The reported genetic risk didn't align with the family history of cancer, and so, the genetic counselor correctly asked to see the patient's genetic test report. When that couldn't be located, the genetic counselor recommended the patient get genetic testing again to confirm that indeed she had a pathogenic variant in BRCA1/2.
Farmer noted that the physician who saw this patient and was considering prophylactic surgeries for a 24-year-old, could have also identified the red flags with careful review of the family history and test report. It appears this didn't happen. "It seems the doctor was considering performing risk-reducing mastectomy and prophylactic ovarian fallopian tube removal in a young woman based on what she reported only," Farmer said. "Even if she were truly 'BRCA positive,' I'd hope there was an in-depth discussion about breast cancer screening options versus surgery, and a nuanced discussion about the timing of ovary removal and effects of surgical menopause on a woman in her 20s. That's earlier than we usually see that done."
When physicians do not have time or are uncomfortable doing the detective work necessary to clarify a case, they should always refer the patient to a genetic counselor, Farmer said.