As sequencing technologies advance, patents expire and legislature addresses health provider inequities, leaders in hereditary cancer genetic counseling, Jill Stopfer, Jessica Coredor and Emily Nazar, discuss the significance of oncological genetic screening and identify potential challenges.
According to Emily Nazar, early genetic testing can benefit the patient and their family members by providing insight into their risk of future cancer diagnoses as well as guiding preventative and targeted treatment. Jessica Coredor notes that some indicators of hereditary cancer in a family genetic history include an earlier age of diagnosis, the same type of cancer or genetically linked cancers occurring throughout generations, and certain cancers with a higher genetic load, meaning they have a greater genetic component.
Genetic counselors are taught to look for patterns, but increasingly tests are conducted based on diagnosis alone. Patients diagnosed with certain cancers identified as having a high genetic load such as pancreatic, ovarian, or metastatic prostate cancers are all candidates for genetic testing, regardless of family history, as there is up to a 20% likelihood of related cancers. Jill Stopfer emphasizes,
“[There are] also an increasing number of publications coming out showing that we don't get the clues that we need so many times by taking a family history. So again, not that the family history is unimportant because sometimes it's screaming at you, or even whispering at you, suggesting that something might be indicated.”
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The source of “possible hereditary risk” is best identified in a family with a strong history of cancer by testing the individual who has had or has the cancer of interest. If a gene alteration is located in the affected member, much information can be gained by testing the entire family.
Challenges arise when individuals who have never had cancer require testing due to a recently diagnosed family member. In this case, an uninformative negative result is not a true negative result, as it does not provide the source of the hereditary risk. Conversely, if the genetic alteration is known from the diagnosed family member, and an unaffected family member’s genetic test is negative, this is a true negative result since it reduces their risk to that of an average person.
Genetic testing can optimize and personalize treatment based on the mutations identified from either the patient’s hereditary genetic profile or mutations found within the tumor. However, early genetic testing is crucial in order to guide oncological treatments, such as the use of PARP inhibitors in breast cancer, as well as secondary cancer prevention. Providers can also apply these genetic testing results to guide pediatric oncological therapies, particularly radiation therapy.
Effective and specialized treatment hinges on expedient testing, and providers can now order a “stat panel” to select for the most critical genes likely to affect a surgical or treatment decision. Previously, such tests could take up to 3 weeks to yield results, compared to a current 7-10 day turnaround that affords providers more personalized treatment plans. Genetic testing can also provide information for early detection and preventative strategies for those at increased risk of certain cancers. For example, early detection of inherited conditions like Lynch syndrome can greatly improve health outcomes as a result of earlier and more frequent cancer screening measures.
Lynch syndrome is the most common inherited cause of colon cancer and also increases an individual’s risk for other cancer types. Once diagnosed, a person with Lynch syndrome would begin their colonoscopies as early as 20-25 years old in order to identify and remove precancerous polyps. Due to National Comprehensive Cancer Network (NCCN) guidelines, most insurers provide coverage of preventative surgeries such as mastectomies if there is a high chance of breast cancer developing, whether increased risk is based on family history or positive genetic markers.
Emily Nazar explains that, at any given clinic, there is usually a consensus among providers regarding which tests are offered to patients, depending on their willingness or hesitancy. A common option is a comprehensive multi-gene panel of about 30-80 genes, from which providers can scale up or down based on findings and patient preferences. Heme panels and solid tumor panels can run larger, especially the latter which can encompass up to 400 genes. When there is a family history of cancer, often only the pathogenic variant is targeted, which can lead to undetected mutations. Jill Stopfer recalls,
“There was a family that looked like a Li-Fraumeni syndrome family, had the classic breast sarcomas, and we found a TP-53 mutation, no surprise you would stop and say there’s the answer! Except, with additional testing, we discovered that this young woman also had a BRCA1 mutation. Now for her particular care, maybe additional information was going to have some minimal additional value, but for the family, figuring out who needed testing for what, it’s a major deal. If we were testing only for one variant and no panel testing had been done we would not have the awareness.”
The Reducing Hereditary Cancer Act, previously H.R.4110, was introduced into the Senate to facilitate access to genetic counseling services for Medicare/Medicaid beneficiaries, which currently excludes preventative genetic testing in patients without a cancer diagnosis. Furthermore, if an individual tests positive for a particular gene of interest, coverage is not guaranteed for follow-up testing. Many diagnosed patients are on Medicare/Medicaid, yet cannot afford the testing they may need to prevent future cancers. Jessica Coredor emphasizes,
“So much of the purpose of doing genetic testing is to help with prevention of future cancers, and if patients don’t have access to that, it puts us in a difficult situation of giving them information that then they don’t have a lot of follow-up that they’re able to do, from a financial perspective.”
Many genetic counselors are rallying for support of bills like the Access to Genetic Counseling Act H.R.2114, since they are not currently considered CMS providers by the Medicare/Medicaid system. The passage of this bill is therefore critical to broader access to genetic care; if passed, genetic counselors would gain recognition as providers from Medicare/Medicaid and eventually, from private insurers. Jill Stopfer elaborates,
“So many institutions have to figure out how to cover the genetic counselors, because the billing has to be…let’s just say, creative. We don’t have the ability to charge our own professional fees, everyone just kind of…sorts it out. But this really is a key piece of legislation in addition to covering the care. For those who have hereditary risk, making genetic counselors part of the medical system in this country is imperative.”
In addition to improving care, The Access to Genetic Counseling Act, H.R.2114, would reduce medical expenses, as genetic counseling is both more economical and targeted than visiting a physician. There have therefore been increased efforts facilitated by the National Society of Genetic Counselors to meet with representatives so they understand the significance of this bill.
Hereditary cancer genetic counselors face a number of challenges as genetic medicine advances and testing becomes standard of care. Some counselors are frustrated by the NCCN guidelines, which are densely worded and often do not identify individuals with clinically actionable mutations. Even though the cost of genetic testing has decreased greatly, the misconception that testing is expensive and unaffordable persists, with the general public unaware that low-income patients are often supported by laboratory guidelines to pay the lowest amount possible. According to Jill Stopfer, future direction would include genetic testing as cancer pathology and oncological care in diagnosed patients, as well as guidelines for family members on hereditary risk. As genetic medicine advances, broad population level genomic sequencing by a general practitioner and at an early age would further individuate treatments. Currently, there are still setbacks to genetic testing, as Jill Stopfer acknowledges,
“Sometimes, some people come to genetic testing seeking clarity, and they walk away with uncertainty. We’re describing alterations in a gene for which our understanding is evolving. There are still people who will look it in the eye and say, ‘I understand what you’re telling me, that this could help guide my care, I don’t want to know.’ And we need to respect those decisions.”
Improving accessibility of genetic testing and proper follow-up requires expansion of the genetic counseling workforce. Currently, there are insufficient counselors or trained providers to offer pre-test counseling to patients. Genetic counselors can help patients navigate an abnormal result that they were unaware they were being screened for, or in the case of younger population screenings, whether it is information they even want to know or feel equipped to digest. Jessica Coredor recognizes,
“I get somewhat hesitant about genetic testing being offered at a population level to patients that don’t know what they’re getting themselves into and don’t know what those results could mean for them, particularly, it can impact your ability to get things like life insurance or disability insurance, and young patients don’t really have a background knowledge of those concepts to even make decisions related to that without some conversations with myself.”
Prior to the identification of cancer-linked genes, hereditary cancer genetic counseling identified risk through methods like linkage, which compares DNA sequences of people who have cancer to the sequences of cancer free individuals to identify commonalities within the affected cohort not shared by their unaffected counterpart, and studies like the tamoxifen cancer study to lower cancer risk. Once these genes were sequenced, gene patenting by companies such as Myriad made testing inaccessibly expensive at thousands of dollars. When those patents were lost, more labs were able to perform sequencing at more affordable rates, and now technologies are rapidly evolving, with next generation sequencing outperforming both linkage and Sanger sequencing.
As genes are increasingly discovered, more tests are available outside of those previously tested. Retesting for individual genes is not necessary, and someone with a previously negative BRCA1 and 2 test can now have additional recommended testing since there have been many more genes identified that impact breast cancer risk. A screening nowadays encompasses at least 12-15 genes and should be covered by insurance as reflected in the NCCN guidelines.
Public awareness of cancer-associated genes has historically played a large role in the accessibility and proliferation of hereditary cancer genetic care. Even though approximately 1 in 280 people have Lynch syndrome, public awareness and discussion of colon cancer is lacking in comparision to high-profile cancers such as breast cancer. Due to celebrity influence and the historical funding of breast cancer research, many people know the BRCA 1 and 2 mutations. While many grants exist for mobile mammogram units, the same does not hold for colonoscopy clinics. In order to improve preventative care for other cancer types, more discussion and resources must be offered to the community to properly educate the public. Genetic counselors must apply their communication skills outside of their fields to educate providers and other health care professionals so that the value of genetic testing is understood.
Historically, genetic ancestry, such as Ashkenazi Jewish ancestry, is often discussed in sessions as there is a higher occurrence of certain mutations in specific ancestral populations. As genetic counseling evolves, ancestry based testing is giving way to a universal approach since many Americans are of mixed ancestry and many more may not know their exact ancestry. In some cases, the approach is useful, as it can help guide decision making for those who are undecided about testing and persuade insurance providers. The ancestral consideration can be lifesaving to some people in populations with higher mutation rates, and some communities are advocating for accessible community testing so that community members have the option of evasive measures. The question of approaching inequitable access and risk assessment based on factors such as ancestry and ethnicity is also a delicate one as oftentimes patient self-reporting is inaccurate.
Some labs are beginning to offer genetic ancestry testing as part of their screenings, which would eliminate the inaccuracies of self-reporting. Additional challenges arise in genetic testing because the genetic database is much larger for those of European vs non-European descent. Replacing ancestry surveys with ancestry markers could improve accuracy, assisting the interpretation of variants of uncertain significance (VUS) and helping genetic counselors identify whether a VUS is a common polymorphism or potentially pathogenic.
Overall, genetic databases require diversification to support the broader community and reflect the US population more accurately. Yearly follow-up with providers and counselors is recommended when a VUS is found, and patients are encouraged to follow-up on their own as provider policies can vary, and providers may not always initiate follow-up.
RNA analysis represents the next evolution of genomic testing, as it enhances test sensitivity when compared to DNA analysis and can be particularly beneficial when investigating splice alterations. Though RNA testing has previously been complicated by the requirement of blood samples, patients can now submit saliva samples for analysis remotely, so that clinic visits are no longer required and accessibility is broader.
The basic tenet of genetic counseling is personalizing advice depending on the significance of the findings and the patient’s background. As new genes are discovered, expansion of the genetic counseling workforce will broaden accessibility to early and individualized genetic cancer care. Genetic counselors face both challenges and opportunities with accelerating technological and legislative advancements, and will benefit from expanded provider status as well as ever-evolving sequencing tools to better serve public health.
View Jill Stopfer, Emily Nazar, and Jessica Coredor’s full conversation on the future of pediatric genetics, available on-demand for free.
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