Clarity, Timing Are Important Factors in the Use of Genetic Testing
The proliferation of cancer-risk gene panels meant to clarify a person’s risks can often create confusion instead.
SAN ANTONIO—The proliferation of cancer-risk gene panels meant to clarify a person's risks can often create confusion instead, warned Susan Mary Domchek, MD, of the University of Pennsylvania in Philadelphia, PA, at the 2015 San Antonio Breast Cancer Symposium.1
“Germline genetic testing is a paradigm for individualized care,” allowing assessment of inherited genetic risks, explained Dr. Domchek. It allows individualized risk assessment, screening, chemoprevention, and preventive surgery—and now, with the FDA's approval of olaparib for BRCA1/2-associated ovarian cancer, personalized therapy.
“BRCA1/2 is the prototype,” said Dr. Domcheck. It's allowed us to learn why an individual is at risk, the significance of a “true negative,” and can help with prevention efforts, she said.
“But we do harm with our interventions, too,” she cautioned. “We need to understand risks and benefits—and timing—of interventions.”
Recent years have seen a proliferation of gene panels for cancer risk assessment. BRCA1 and BRCA2 tests are rare variants with high relative-risk implications for a patient's risk of cancer, and CHEK2, ATM, and NBN represent rare variants associated with a moderate relative-risk, Dr. Domchek noted.
But increasingly, single-nucleotide polymorphisms (SNPs), which are very common variants that tend to convey low or questionable relative risks for cancer, are also being added to gene panels for cancer risk assessment, Dr. Domchek warned.
“There are more than 100 breast cancer SNPs now, and gene-testing panels are increasingly more complicated,” she said. Several SNP panels, including “23andMe,” are no longer available. But others still are, and they've caused some confusion, she said. More than a dozen such panels are on the market.
“There are tests available for all of this and we're still trying to understand what to do with it all,” she said. SNPs are not comprehensive gene sequencing like BRCA1/2, she emphasized, and should not be used as a stand-alone test for people with a strong family history of breast or ovarian cancer.
It's unclear what their clinical utility or actionability will be. Results can vary between panels or “be given different attributions across different labs,” Dr Domcheck warned.
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“Patients need to understand when there is uncertainty and that these are largely different [tests] from BRCA1/2,” she urged.
“Patients and providers can get confused about SNP panels,” she warned, illustrating the point by describing a case in which the cousin of a patient was found to carry a deleterious BRCA2 mutation, prompting the cousin to seek testing by her gynecologist. But when the test results came back, reporting a 13% lifetime risk of cancer, it turned out the wrong test had been ordered. The test results were not for a BRCA1/2 test at all, but a SNP panel that has no bearing on inherited BRCA mutation-associated cancer risks.
- Domchek SM. Interpretation of genetic tests and management of patients. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 8, 2015; San Antonio, TX.