Seven diseases benefiting from genetic tests


Genetic testing is playing a growing role in diagnosing and treating diseases, particularly when it comes to certain cancers and rheumatic conditions.

Genetic testing is playing a growing role in diagnosing and treating diseases, particularly when it comes to certain cancers and rheumatic conditions. An FDA decision in November 2017 to approve the use of a multi-gene panel to evaluate more than 300 genes in cancer tissue will ensure even broader use of these promising treatment approaches.

“The FDA’s move will lead MCOs to appraise the clinical utility of these new tests to help determine future healthcare coverage and cost implications,” says Phil Smalley, MD, FRCPC, chief medical director, Wamberg Genomic Advisors, a genetic testing consulting firm and provider.

CMS has already proposed coverage for the test, the FoundationOne CDx (F1CDx).

Smalley says potential benefits of genetic testing of cancer tissue specifically include:

  • Sharper diagnostic accuracy
  • Improved treatment selection using precision medicine
  • More patients enrolled in clinical trials and new cancer drug discoveries
  • Better predictions regarding patient survival and improved survival
  • Fewer cases of cancer occurring in family members

Many studies have already shown that personalized oncology therapies based on tumor genetic biomarkers improve patient outcomes, Smalley says. Even in end-stage cancer patients, some studies show that genomic profiling guided targeted therapies can benefit patients. The recently published Moscato trial showed that 49% of solid tumors carry at least one actionable genetic mutation that can be treated with existing targeted drugs directed at cancers with those specific genetic alterations.

Here’s a closer look at cancers and other conditions benefiting from genetic testing and biomarkers.

Breast cancer


An inherited gene mutation increases risk for breast cancer up to five times the average lifetime risk, says Emily Kuchinsky, MS, certified genetic counselor, Medstar Cancer Network, Baltimore. Approximately 5% to 10% of breast cancers are inherited.

The most common gene mutations related to breast cancer are found in BRCA1 and BRCA2 genes. Carrier women are advised to undergo breast MRIs starting at age 25 and mammograms at age 30. These women could also consider breast removal, which reduces breast cancer risk by more than 90%, according to National Comprehensive Cancer Network’s (NCCN) guidelines.

Women already diagnosed with breast cancer in one breast may consider removing both breasts because BRCA carriers have up to a 50% chance of developing cancer in their second breast in their lifetime, Kuchinsky says.

The public’s demand for genetic testing for breast and ovarian cancer jumped 64% after actress Angelina Jolie openly announced that she carries a BRCA1 mutation, according to Harvard researchers. But because less than 1% of Americans carry a BRCA1/2 mutation, patients should meet with a genetic counselor to determine if they are good testing candidates before undergoing testing, Kuchinsky notes.

In 2013, the U.S. Supreme Court ruled that genetic testing laboratories could not patent BRCA1/2 genes. This ruling allowed any laboratory to test for BRCA1/2 and has driven down the overall cost of genetic testing for cancer risk genes, Kuchinsky says.

“By assessing cancer risk accurately, high-risk individuals are identified and can be offered increased screening and preventative options,” Kuchinsky says. “This reduces overall healthcare costs by lowering cancer incidence or allowing cancer to be detected in early stages which requires less treatment.”

Next: Prostate cancer



Prostate cancer

Genetic testing is also being used to identify inherited genetic mutations related to prostate cancer, particularly among men with metastatic prostate cancer, says Veda N. Giri, MD, associate professor and director of cancer risk assessment and clinical cancer genetics, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia.

If a man undergoes genetic testing and an inherited mutation is identified, his male and female family members may want to consider genetic testing to identify cancer risks and screening recommendations, Giri says. Men with BRCA1 and BRCA2 gene mutations are currently recommended by the NCCN to have prostate cancer screening starting at age 45. Tailoring screening for prostate cancer based on genetic test results has the potential to reduce the cost of care.

Genetic information is also being used to select specific patients for certain therapies, called precision medicine, such as PARP inhibitors for men with a BRCA gene mutation or DNA repair gene mutations, Giri says. This type of treatment has the potential to provide the right care to the right patient.

Non-small cell lung cancer


Each patient’s cancer is unique. Providers need knowledge about the genetic makeup of an individual’s cancer and its micro-environment to best tailor care, says Abhisek Swaika, MD, board-certified oncologist/hematologist, Queens Medical Associates, Queens, NY.

For patients with advanced stage/metastatic non-small cell lung cancer, NCCN recommends testing for specific biomarkers in tumor samples. Treatment is then appropriately selected for any specific mutations detected, says Swaika. Some specific biomarkers include EGFR, ALK, ROS-1, PD-L1, and the BRAF mutation-which was just approved by the FDA as a biomarker in June 2017.

“Drugs developed to target these specific indicators have demonstrated better results than traditional chemotherapeutic agents,” Swaika says. “Side effects differ and are generally more manageable and often less severe. Patients’ quality-of-life measures are also reportedly better.”

Ongoing research to validate these tests in blood samples, also referred to as liquid biopsies, may help to eliminate the need for tissue biopsies, thus decreasing the risk of invasive procedures and lowering healthcare costs Swaika says.

Biomarker testing on lung tumor samples has become more readily available and standardized as advocated by national guidelines, so reimbursement opportunities are growing and there is increased use, Swaika says.

Next: Melanoma




Biomarkers for melanoma help identify patients most likely to benefit from therapy and least likely to suffer unusual or severe toxicities, and they generate increased value, says Michael V. Seiden, MD, PhD, senior vice president and chief medical officer, The U.S. Oncology Network and McKesson Specialty Health, an organization focused on provider, practice management, biopharma, and payer solutions.

Melanoma has had two revolutions in biomarker discoveries. The first was based on a key genetic finding in 2002 when it was discovered that a specific mutation in the BRAF gene, found in half of individuals with melanoma, led to changes in its associated protein and promoted tumor growth, Seiden says. BRAF is a kinase (a type of enzyme) that modifies other growth promoting proteins. Targeting this protein with a drug called a kinase inhibitor and a second drug that also prevents growth (also a kinase inhibitor) has been effective in most individuals with mutations in BRAF.

A genetic test evaluating the BRAF gene is highly predictive of which patients will experience at least temporary benefit from kinase inhibitors and therefore eliminates the cost of giving these drugs to patients who won’t benefit, Seiden says.

Presently, more attention is being focused on oncology immunotherapy, i.e., the use of the immune system to treat cancer, by using immune checkpoint inhibitors, Seiden says. Still in development, they show even greater promise than kinase inhibitors.

About half of patients with advanced melanoma will respond to immunotherapy, so it is now common for all patients with advanced disease to try these agents.

About one in five individuals with advanced melanoma have been cancer free for more than three years, with some patients having been cancer free for almost a decade, suggesting that new immuno-oncology agents might cure certain individuals with metastatic melanoma.

But Seiden says there is an urgent need to determine who will achieve maximum benefit from one immunotherapy drug and which patients will only benefit from the combination of two or more drugs (all of which are very expensive and toxic). In addition, tests that might identify the subset of patients who won’t benefit from these therapies and hence might be spared the cost and risks of therapy have yet to be developed. 

Next: Hereditary colon cancer



Hereditary colon cancer

Individual cancers may occur as a manifestation of a genetic cancer syndrome, which are treated differently than those that aren’t genetic due to higher probabilities of recurrent cancer as well as secondary cancers associated with specific genetic syndromes, says Richard P. Frieder, MD, cancer geneticist and director of the Women’s Cancer Prevention Program, John Wayne Cancer Institute at Providence Saint John’s, Santa Monica, CA. 

Colon cancer is known to have a hereditary predisposition in at least 5% of cases. More than 15 cancer syndromes may present with colon cancer as the initial malignancy in a syndrome, of which a patient and their family members may be at risk, Frieder says. The most common syndromes include Lynch, familial adenomatous polyposis, Li-Fraumeni, Cowden, Peutz-Jeghers, POLD1, POLE, and GREM1.

Given the estimated cost of treatment, the cost of genetic risk assessment is highly cost effective, Frieder says. Most laboratories charge $500 to $2,000 for this type of genetic testing for colon cancer and other genetic cancer syndromes.

Patients with inherited genetic syndromes that predispose them to cancer can benefit from earlier diagnosis with improved morbidity and mortality rates. Primary prevention is possible for most common inherited cancers such as breast, ovary, colon, and uterine, Frieder says, but this is only possible for individuals who are aware of their genetic mutations and the associated cancer risks.

Secondary prevention is possible for patients who have already been diagnosed with one type of cancer, who are concerned about preventing another type of cancer which may be associated with their genetic syndrome, Frieder says.

Rheumatoid arthritis

Biomarkers are also being used to detect and monitor certain rheumatology conditions. Catherine H. MacLean, MD, PhD, rheumatologist and chief value medical officer, Hospital for Special Surgery, New York, says biomarkers are used to help diagnose rheumatoid arthritis and track and treat disease activity, which in turn can prevent joint damage.

Rheumatoid factor (RF) and antibodies against cyclic citrullinated proteins (anti-CCP) are biomarkers that are routinely used to establish a diagnosis of rheumatoid arthritis, and are part of the 2010 American College of Rheumatology/European League Against Rheumatism criteria for its diagnosis. A number of other biomarkers are under investigation, but their utility in clinical care has yet to be established.  

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are two biomarkers that can specifically indicate inflammation and other disease indicators. “These biomarkers may be used alone or in combination with several other parameters to measure disease activity, which is used to direct therapy,” MacLean says. “Higher levels may lead to increasing drug dosages, adding additional drugs, or changing drugs in a treatment regimen. Conversely, low disease activity may result in lowering doses or stopping drugs.”

Biomarkers in rheumatoid arthritis impact costs by identifying disease activity early, allowing for aggressive treatment, and preventing joint damage, which can lead to disability and expensive joint replacements. They can also identify patients at risk for certain disease comorbidities (e.g., ophthalmic disease, rheumatoid lung disease) and aid in selecting drugs that will be effective for specific patients.

Next: Lupus





Biomarkers have been used in lupus to help physicians better monitor disease status, treat flare-ups before they occur, and determine which treatments will work best in each patient and when to use them, says William V. Williams, MD, FACP, president and CEO, BriaCell Therapeutics Corp., which develops novel immunotherapies to fight cancer; and adjunct professor of medicine, University of Pennsylvania, Philadelphia. They may also indicate if a treatment is working or producing side effects before they become apparent from how the patient looks and feels. 

Some biomarkers, known as anti-nuclear antibodies (ANAs), help physicians figure out what type of lupus a patient has-since many types exist, Williams says. This helps physicians to make treatment decisions and also helps them to figure out which organs (such as the kidneys or skin) might become affected by the disease.  

Biomarkers increase patients’ quality of care by anticipating flare-ups. Markers of inflammation, called “complement” components, go up and down in blood tests depending upon inflammation levels. Sometimes they go down before a lupus flare-up, Williams says, so physicians will treat the patient to prevent a flare-up. This is also true of anti-DNA antibodies, which can increase before a flare-up and decrease when a patient is improving. Newer biomarkers, such as interferon signature biomarkers, help to select which patients will benefit the most from new treatments being developed.

Biomarkers in lupus help reduce healthcare costs by allowing physicians to better monitor patients, providing treatments before the disease becomes too severe-avoiding costly hospitalizations, Williams says. They also help by predicting if a patient is going to have a flare-up, so they can be treated before the disease gets so severe that the patient has to be hospitalized or develops kidney failure and has to go on dialysis.

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