Date: October 28, 2017
Author: Elaine Schattner
A horrifying story broke last week about a 36-year-old Oregon woman who had elective surgery to remove her uterus and breasts. Elisha Cooke-Moore underwent a prophylactic total hysterectomy and bilateral mastectomy, with nipple-sparing reconstruction and implants, after medical practitioners informed her she had cancer-causing genes. Only later, she learned she didn’t have the abnormality about which she’d been informed. There’s a lawsuit.
As reported in The Washington Post, Cooke-Moore expressed concerns to a doctor about her family’s cancer history before getting tested for mutations in BRCA-1, BRCA-2 and related genes in 2015. A nurse practitioner reviewed the results and erroneously told her she had Lynch syndrome because of an MLH1 mutation. BRCA testing was “negative.” It’s not clear if any doctor directly reviewed the lab report. An obstetrician-gynecologist informed Cooke-Moore that her chances of developing breast cancer were 50% and for uterine cancer up to 80%. In 2016, at least two surgeons operated.
Cooke-Moore discovered the mistake while looking over her medical records: The MLH1 result was “negative,” she noted in 2017. “I am damaged for the rest of my life,” Cooke-Moore told The Washington Post.
Never mind the specifics. While it sounds like the plaintiff received egregious care, and I am sympathetic, I see this as a larger story of confusion over genetic test results leading to irreversible harm. My aim here is not to probe Cooke-Moore’s results or the circumstances of her decisions, but to consider the lessons for other patients and doctors. This case should be a wake-up call about the quality of DNA testing and what variable guidance patients receive about their results. The implications are broad.
Checking genes for presence or absence of mutations is not straightforward as you might think. Mutations vary: They’re rarely “positive” or “negative,” end of story. Some doctors may not fully appreciate the nuances of genetic findings. While some DNA abnormalities are clearly linked to disease, such as mutations tied to cystic fibrosis or sickling of hemoglobin, often there’s a range of severity of illness and pathology among affected patients. Among the cancer risk genes, BRCA-1 and -2 are probably the best studied. Yet even for those, doctors don’t yet understand why some people who inherit BRCA mutations don’t develop cancer, i.e., what mitigates disease risk. Some changes are deemed variants of uncertain significance.
Given the enormity of this subject, I’ll focus on three practical measures to reduce regrettable outcomes after testing for cancer genetic risk.
- If you consider getting tested for familial cancer risk, ask where your sample will be evaluated, and exactly what genes will be tested.
The practitioner may or may not know the answer to these questions. But part of the point of asking is to ensure that the responsible physician or genetics counselor is clued in to the details because gene testing companies vary in their methods, which gene variants they report, how fully they report on those, and how they interpret any detected abnormalities.
Some companies, like Myriad Genetics, focus on BRCA and related cancer risk-associated genes. Myriad offer various testing panels to assess hereditary cancer risk. Some large and more general commercial laboratories, like LabCorp and Quest Diagnostics, offer BRCA-related panels (BRCAssure and BRCAdvantage, respectively). Ambry is another player in this field. More recently Color Genomics, a San-Francisco based company, entered the fray; they’ll check your BRCA status for less. Some universities and hospitals offer “in house” testing.
These labs (and this is not a comprehensive list) use distinct and sometimes proprietary ways of extracting DNA from samples, amplifying and analyzing genetic material. They employ different scientists who develop methods and interpret results variously in context of the rapidly-growing literature on cancer risk and cancer-related mutations. The doctor who orders genetic tests should be aware of these possible differences.
At the minimum, before making any decisions I’d want to know that my test was performed in a CLIA-certified laboratory.
- Before taking any treatment based on a genetic test result, hit the pause button. Get a copy of the full report and keep it. Ask questions. Try to get a second opinion.
Before agreeing to anything so drastic as prophylactic surgery, or taking medication aimed at reducing cancer risk, you might want to have the test repeated, to confirm or supplement initial results. Even nonprescriptive changes, like adjusting your diet, or participating in a clinical trial for people with specific genetic variants, carries possible benefits and risks. You might wind up taking a medicine, or getting screened in a way that you would not have otherwise.
Among the questions I’d want to ask a doctor are these: “How confident are you about the accuracy of my test result?” and “What are the implications for my health?”
Whenever possible, get a second opinion before a major procedure or treatment is implemented. Ideally, advice would come by a physician familiar with both the nitty-gritty of DNA testing and the relevant medical condition. Keep in mind, experts may have informed but distinct and biased perspectives on the significance of an abnormality, such as an MLH1 mutation. The most knowledgeable physicians may not have ready answers when it comes to interpreting DNA findings in context of an individual patient with a unique medical history and concerns. Consulting with a genetics counselor may also be helpful.*
- Use the web and other resources, including patient-oriented organizations, to learn what you can about your genetic results.Here’s a partial list of societies and websites that provide information about genetic testing for cancer risk:
Cancer.net offers information about hereditary cancer syndromes that is provided by the American Society of Clinical Oncology;
FORCE (Facing Our Risk of Cancer Empowered) is a patient-oriented organization with many resources and detailed information for people affected by a familial disposition to developing breast, ovarian and other cancers;
The National Cancer Institute’s Genetics of Cancer page includes numerous links to NIH resources for particular cancer risk genes and syndromes;
National Society of Genetic Counselors details the role of genetic counselors and refers to several resources for patients;
The American Society for Human Genetics is a professional organization that offers general information on gene testing and links to additional resources.
I’m constantly amazed at the explosive field of diagnostic human genetic testing. Despite my concerns about the quality and guidance of interpreting results, I’m impressed by the power of diagnostic human genetic testing. For people who are ill, gene testing can be enormously helpful in establishing the cause of disease, pinpointing a diagnosis, and in some situations knowing how best to treat a medical condition. For those who have reason to worry about inheriting a disposition to disease, gene testing could offer life-saving information about pre-emptive or risk-reducing interventions. In each of these circumstances, informed guidance provided by doctors — in interpreting results and in clinical decision-making — is crucial.