Incorporating Genetics into Clinical Care

TON - July 2017, Vol 10, No 4 - Survivorship
Chase Doyle

San Diego, CA—Guided by advances in genomic technology, healthcare has entered the era of precision medicine. With genetic testing now standard of care in oncology practice, cancer is at the forefront of this initiative, but providers still face many concerns. At the recent Cancer Survivorship Symposium, Angela R. Bradbury, MD, Assistant Professor, Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and Christine Miaskowski, RN, PhD, FAAN, Professor, Physiological Nursing, University of California San Francisco School of Nursing, outlined benefits and limitations of genetic testing, its evolving role in survivorship care, and possible implications for symptom management.

“Precision medicine will provide many great opportunities to improve cancer care and survivorship care, but we’re going to have to tackle some of these challenges and work together to come up with best practices,” said Dr Bradbury. One of these challenges is integrating genetic assessment into survivorship care.

Research has shown that identifying carriers of BRCA1/2 genes provides opportunity for life-saving surgery, and colonoscopy has been shown to reduce colon cancer mortality in patients with Lynch syndrome.

“Genetic testing can be critical for identifying mutations associated with increased risk of cancers, and should be listed in survivorship plans. Recent data demonstrate clear clinical utility,” said Dr Bradbury.

Who Is Getting Tested?

Although the classic features of genetic predisposition—early-onset cancer, bilateral cancer, multiple primaries, rare cancers, adrenal cancers, and cancer syndrome pairs—are still incentives for testing, with the advent of multigene panel testing and the decreasing costs of germline genetic testing, “these criteria have become somewhat antiquated,” Dr Bradbury acknowledged.

“Multigene panels have thrown the cancer genetics world upside down. We’re testing so many people now, and so many people are getting coverage. You can get a whole panel for $475 or less,” she said.

Multigene panels test anywhere from 5 to 40 genes, and cover a wide variety of cancers. Whereas some genes on the panel have very high risk for cancers and have established guidelines, others are moderate-risk genes, which may not alter a patient’s care.

“There are still genes we don’t know much about,” said Dr Bradbury.

Analysis of the first 10,000 patients who had undergone multigene panel testing at a single commercial laboratory showed that approximately 10% of cancer survivors had positive results, with half of mutations identified in moderate-risk genes.

“That’s important, because those are the settings where guidelines are either nonexistent, emerging, or rapidly changing. This creates a real challenge for cancer care providers. If you’re having continued follow-up, the survivorship setting is a good place to revisit recommendations that were made and see what might have changed in the literature because they could be totally different,” said Dr Bradbury.

How Often Does Testing Change Care?

In a study of 1000 BRCA1/2-negative women who had undergone multigene panel testing, 62 were identified as carriers. Of these carriers, 33% had mutations in genes with established guidelines, leading to a change in their medical management.

“Clearly, there was clinical utility for that subset. In 66% of carriers, in whom moderate-risk genes were identified, medical management changed only 25% of the time,” said Dr Bradbury.

The Risk for Uncertainty

Testing positive for mutations that carry known risk is not the only concern. Thirty percent of multigene tests identify a variant of uncertain significance.

“The overwhelming majority of these get reclassified to benign changes over time, but a variant of uncertain significance can become clinically significant. It’s important for patients to be aware of these variants, too,” said Dr Bradbury.

Given these uncertainties, patients should know “what they’re getting into” with multigene panel testing. That is, providers should share with patients the benefits and the limitations of the procedure.

“The largest limitation or risk is the potential for uncertainty. If a patient is not good with uncertainty—if that is going to unglue them—it might be better to do a targeted panel and revisit the multigene panel later,” said Dr Bradbury.

Improving Access to Genetic Counseling

As the complexity of clinical testing increases, collaborating with genetic counselors can help bridge this knowledge gap. For providers without access to genetic counselors, Dr Bradbury recommended partnering with other academic institutions and considering novel delivery models. The Penn Medicine Abramson Cancer Center Telegenetics Program, for example, offers genetic counseling by phone or real-time video conferencing.

“We partner with community hospitals that don’t have genetic counselors on staff. This is a model that has worked very well, and we’ve been able to expand testing to underserviced areas,” said Dr Bradbury.

Symptom Management in Cancer Survivors

According to Dr Miaskowski, the hope of precision medicine is to use genomics to stratify patients to receive tailored treatment. This tailoring presents a major challenge, however, as studies have shown that cancer survivors report between 9 and 15 symptoms on average.

“We need more epidemiological studies for individual symptoms and multiple co-occurring symptoms in people who survive cancer treatment,” said Dr Miaskowski.

Variability estimates differ considerably in the literature, in part because of the instruments used to assess symptoms. The Memorial Symptom Assessment Scale contains 32 symptoms, and the M.D. Anderson Symptom Inventory contains 13 symptoms, yet only 7 of these symptoms are overlapping. Moreover, these instruments have not been updated to capture symptoms associated with newer therapy.

“People are highly variable in presentation and how they respond to treatment. That’s the goal of precision health: to understand this variability and group people in a way that we can predict individuals with higher symptom burden,” said Dr Miaskowski.

Genomic Predictors of Fatigue

Research establishing the relationship between genomics and symptom severity has largely been focused on fatigue. The theoretical model suggests that fatigue associated with cancer and its treatment is a complex phenotype.

One study that compared patients with moderate to very high levels of fatigue identified several differentially perturbed pathways, including inflammation, immune function, circadian rhythm, renal function, neurotransmission, skeletal muscle energy, and carbohydrate metabolism.

A separate study identified several phenotypic predictors of higher evening fatigue, including younger age, female sex, poorer functional status, and worse comorbidity profile, among others.

“These phenotypes typically predict a higher symptom burden, as well. I would encourage providers to think about these predictors as they see survivors,” said Dr Miaskowski.

Co-Occurring Symptoms: Who Is at Risk?

Patients with cancer and cancer survivors rarely present with a single symptom. Clinical experience suggests that significant variability exists among patients’ and survivors’ symptom experiences.

“We need to determine what demographic, clinical, symptom, and genomic characteristics predict a higher symptom burden, but it’s also important to evaluate for protective factors in patients with a lower symptom burden. Low groups may have protective factors that could be mined as therapeutic targets,” Dr Miaskowski explained.


Dr Miaskowski urged clinicians to conduct routine assessments of the most common symptoms in cancer survivors, such as fatigue, pain, sleep disturbance, cognitive impairment, and changes in mood. The most important action for the community, however, is to urge healthcare systems to include symptom data in the electronic health record.

“If we can’t integrate symptom data with all the other treatment data, it’s going to be very challenging to move this work forward,” she said.

“Finally, I would encourage all the collaborate with colleagues to conduct symptom management studies,” Dr Miaskowski concluded.

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Last modified: August 7, 2017