A novel, automated liquid biopsy test in development by researchers at the Johns Hopkins Kimmel Cancer Center can accurately detect the presence of cancer DNA in the blood of patients with metastatic breast cancer within five hours. The test, currently a prototype for research use only, potentially could be used to quickly help oncologists determine if cancer treatments are working.
The test, called the Liquid Biopsy for Breast Cancer Methylation (LBx-BCM), is compatible with a commercially available molecular testing platform called GeneXpert® and can detect methylation, a type of chemical tag, in one or more of nine genes altered in breast cancers in 4.5 hours. It requires less than 15 minutes of hands-on time by a laboratory technician. A validation of the test and its potential uses was published online May 6 in the journal Cancer Research Communications.
Many patients with breast cancer do not respond to chemotherapy but go through multiple cycles of treatment before oncology teams can perform imaging studies to determine if a treatment is effective, explains senior study author Saraswati Sukumar, Ph.D., professor of oncology and pathology at the Johns Hopkins University School of Medicine. Imaging can be effective at detecting changes in larger tumors, but it is nearly impossible to identify changes in smaller tumors, Sukumar says.
Our goal was to develop an assay that would be sophisticated yet simple to perform worldwide and could be used at the point of care to provide same-day feedback to clinicians and patients. If we are able to show by this cartridge assay that we are indeed successful in predicting the course of treatment, we might be able to institute changes in the way we look at chemotherapy and the way we treat patients for…
In this interview, we speak to Sheetal Parmar, vice president of medical affairs and head of clinical services at Natera, about their cell-free DNA (cfDNA) testing services and the future of genetic testing with science.
Please could you introduce yourself and tell us about your current role at Natera?
I’m Sheetal Parmar, a board-certified genetic counselor and vice president of medical affairs at Natera.
Natera is a global leader in cell-free DNA (cfDNA) testing. What are some of your aims and missions at Natera?
At Natera, we aim to make personalized genetic testing and diagnostics a part of standard care, and our mission is to change the management of disease worldwide. Our core cfDNA technology provides health information in the areas of reproductive health, oncology, and organ health.
Natera is revolutionizing the standard of care with next-generation, cell-free DNA testing
You analyze cfDNA to find insights about health and disease. What is cfDNA and what insights can you gain from analyzing it?
Cell-free DNA, or cfDNA, are small pieces of free-floating DNA found in the bloodstream. Everyone has cfDNA that originates from their own cells in their bloodstream. By analyzing the cfDNA from a blood draw, we can collect useful genetic information about a variety of conditions.
The first application of our cfDNA technology was in the reproductive health space. During pregnancy, there is cfDNA from both the pregnant individual and the placenta circulating in the bloodstream and we can analyze it to screen for chromosome conditions such as trisomy 21, trisomy 18, and trisomy 13.
We applied what we learned about analyzing cfDNA during pregnancy to oncology to detect molecular residual disease and monitor disease recurrence, and also use this technology in organ health, to assess for transplanted kidney, heart, and lung rejection.
Despite women’s health seeing more interest in recent years, there is still more that needs to be done. What do you currently believe to be some of the biggest challenges faced by women’s health and why should life sciences companies be placing a greater emphasis on it?
I agree that there is so much more we can do to address challenges in women’s healthcare. For example, despite all our scientific advances, there exist pregnancy complications such as preterm birth and preeclampsia that are associated with morbidity and mortality. Preterm birth affects about 10% of pregnancies and is associated with significant neonatal morbidity and mortality.
Preeclampsia, a condition where a pregnant person develops high blood pressure with protein in the urine and other problems affects approximately 3-8% of pregnancies. 10-16% of maternal deaths in economically advanced societies are due to preeclampsia. Many researchers and companies are focusing on health issues like these because they are significant and methods to identify pregnancies at risk are limited.
Natera has developed a variety of tests within the field of women’s health. Can you describe some of the tests that are available for women and what they test for?
Natera has a number of genetic tests that provide important health information from preconception through pregnancy. This includes Spectrum preimplantation genetic testing of embryos during the IVF process; Horizon carrier screening for individuals and couples to determine their risk for passing a genetic condition to their child; Panorama NIPT which screens for chromosome conditions in the pregnancy, Vistara NIPT which screens for single-gene conditions in the pregnancy, and Anora which is a test on miscarriage tissue to identify the cause of a pregnancy loss.
Additionally, we have a genetic test called Empower for those who want to know more about their risk for developing cancer, understand why it might be more common in their family, or want to inform treatment options following a cancer diagnosis. Empower screens for genes associated with an increased risk for common hereditary cancers and our multi-cancer panels include commonly screened-for genes associated with 12+ types of cancer.
Image Credit: 10 FACE/Shutterstock.com
You have also applied your technology to noninvasive prenatal testing (NIPT). Can you tell us more about NIPT and why it is beneficial not only to the mothers but to research also?
For a pregnant person, knowing their baby’s risk for certain genetic conditions allows them to prepare. NIPT is a screening test and not a diagnostic test. This means it can tell you what the chances are for certain genetic conditions in the pregnancy. While this test is not diagnostic, having a low-risk result for the conditions screened can provide some reassurance.
For a high-risk result, a confirmatory diagnostic test is recommended and this can be done during the pregnancy or after delivery. Knowing that a pregnancy has a genetic condition can inform what type of hospital a person should deliver at, what medical specialists should be available after delivery, what treatments or interventions might be recommended, and gives people time to prepare emotionally. In some cases, it can prevent a long diagnostic odyssey. For example, the average years to diagnose 22q11. 2 deletion syndrome is 4 years. We can now screen for 22q11.2 with cfDNA.
From a research perspective, Natera is committed to peer-reviewed publications for all our tests. I’m proud to say there are over 100 peer-reviewed publications across all our products and 25 of those are specific to Panorama NIPT. We recently published the results of the SMART study which is the largest prospective NIPT study ever conducted in a general population.
One of the reasons we sponsored this 20,000 patient study was to confirm Panorama test performance in the general population, which we did. However, more importantly, this study provided information on the incidence and test performance of 22q11.2 deletion syndrome. Individuals with this condition can have heart defects, immune deficiency, low calcium levels, cleft palate, learning differences, and schizophrenia.
With this study, we confirmed that this condition is not rare, in fact, in this cohort we found that the incidence was approximately 1 in 1500 pregnancies, which is more common than other conditions routinely screened in pregnancy. This peer-reviewed published data supports offering screening for 22q11.2 deletion syndrome to all pregnant individuals.
You are currently pushing the boundaries of testing management within science. How important is innovation to the field of genetic testing?
Innovation is incredibly important to translating advanced genetic technologies into usable and informative tests for the general public. One example of innovation from Natera’s R&D team is the application of AI to the Panorama algorithm.
Through analyzing millions of tests, the Panorama AI algorithm was able to reduce the number of “no results” while maintaining high test sensitivity and specificity. We also applied algorithm improvements to NIPT for 22q11.2 deletion where we improved our detection of various deletion sizes and increased the positive predictive value of the test from 20% to 53%.
However, innovation applies to more than the tests. It’s important to the overall infrastructure of testing. How easy is it for a healthcare provider to order the test and get results? Do patients and ordering providers have access to education and information during the entire testing journey? We wanted patients to have access to our genetic education services 24/7, so our genetic counseling team worked with our user experience and engineering teams to build NEVA, Natera’s educational virtual assistant. This is a chatbot that can provide pre-test education as well as post-test result information across many of our products.
Patients can even schedule an appointment with a Natera genetic counselor through NEVA. About 30% of patients use this outside of normal business hours, which means NEVA helps patients access information when it’s most convenient for them.
Image Credit: Natali _ Mis/Shutterstock.com
What do you believe the future of reproductive genetic testing looks like? Are there any particular trends that you foresee?
We are moving towards having the ability to screen individuals and pregnancies for a larger number of conditions. We have seen this across preimplantation genetic testing, carrier screening, and NIPT. Of course, it’s critical that as expansion occurs, there is a high level of test performance and that genetic education and counseling be available to anyone interested in testing. Equitable access to testing is necessary as well.
Do you believe that with continued innovation at Natera, you will continue to change the ways that diseases are managed? What would this mean globally?
As Natera continues to explore the potential applications of cfDNA, this could definitely have an impact on disease management and treatment. There are several studies currently looking at the need for chemotherapy for colorectal cancer patients based on the presence of ctDNA, or tumor fraction of cfDNA, regardless of cancer stage.
Also, the Prospera transplant assessment test is able to monitor for solid organ transplant rejection more accurately than existing biomarkers. Since rejection is the most common cause of transplant failure, early, more accurate detection will have a significant impact. Globally, these tests could impact the treatment and monitoring of both cancer and transplant patients and optimize treatment.
What is next for Natera? Are there any exciting projects that you are involved in?
The women’s health division is collaborating with clinicians to engage in clinical research aimed at improving and expanding the Panorama NIPT product. We are also looking at ways to improve overall maternal/fetal health during pregnancy through early identification of potential perinatal complications. I’m also really excited about partnering with our newest business unit for early cancer detection.
Where can readers find more information?
Natera’s website has a wealth of information for both patients and clinicians. We run a women’s health blog, as well as host videos, peer-reviewed research, and webinars.
About Sheetal Parmar
Ms. Parmar is vice president of medical affairs and head of clinical services at Natera. She is a board-certified genetic counselor specializing in prenatal diagnosis and screening. Sheetal received her BA in Molecular and Cell Biology from UC Berkeley and her MS in Genetic Counseling from the University of Cincinnati, where she was a Albert C. Yates Scholar and Fellow. She joined Natera after working for 11 years as the lead prenatal genetic counselor at a high-risk prenatal diagnosis clinic and cytogenetic laboratory.
She has served on the Board of Directors for the National Society of Genetic Counselors (NSGC) and is currently a site visitor for the Accreditation Council of Genetic Counseling (ACGC). In 2020, Sheetal received the Leading Women Entrepreneur Force for Change Illuminator award for her contribution to Natera’s positive impact on the lives of others during the COVID-19 pandemic.
Colorectal cancer is the third-most-common cancer in both men and women in the United States and is the second-most-common cause of death from cancer, behind only lung cancer. Because most cases of colon cancer take years to develop, we have an opportunity with regular screenings to not only catch cancer at an early, curable stage, but with colonoscopy, we can also remove the precancerous polyps and prevent cancer from developing.
As we commemorate Colorectal Cancer Awareness Month, I want to make sure everyone is aware of the latest guidelines on colorectal cancer screening. In 2021, the U.S. Preventive Services Task Force updated its recommendations on colon cancer screening to offer screening at age 45 for all average-risk adults. Part of the rationale to lower the age for screening is that despite improvements in the overall trends of colon cancer cases and deaths over the past few decades, we have seen as much as a 15% increase in the number of colorectal cancer cases in adults ages 40 to 49.
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While we say that the best screening option is whatever test has the highest likelihood of a patient completing it, there are two major testing approaches most often used in the U.S. that are supported by the highest-quality evidence: colonoscopy and stool-based testing.
The benefit of a colonoscopy is that it is both diagnostic and therapeutic. This means that whatever we find during the screening, such as precancerous polyps, we remove at the time of screening.
Stool-based testing strategies, such as an annual fecal immunochemical test (FIT) or a multitarget stool DNA test every three years, are also highly effective strategies. However, stool-based testing is considered a two-step strategy, because any positive test still requires a colonoscopy for follow up to remove any polyps. Less commonly used screening tests include flexible sigmoidoscopy, CT colonography or colon video capsule. These tests do not have as much evidence supporting their use and should be reserved for patients unable or unwilling to undergo colonoscopy or annual FIT testing.
When deciding which screening approach to use, patients should also consider their overall risk for colon cancer. Stool-based testing should only be used by “average-risk” patients, so anyone at higher risk for colon cancer based on a personal history of colon polyps, a family history of colon cancer or an underlying medical condition such as inflammatory bowel disease should not use a stool-based screening option and should instead undergo a colonoscopy. Depending on a patient’s risk factor, the age at which to start screening could be younger than 45, and this decision is best made with the input of a primary care physician or a gastroenterologist.
How UVa Cancer Center can help
The UVa Cancer Center — one of just 52 National Cancer Institute-designated comprehensive cancer centers in the U.S. and the only one in Virginia — offers exceptional screening and care for colorectal cancer. UVa provides the full range of colorectal cancer screening options for patients, including high-screening colonoscopy to patients, as well as diagnostic colonoscopy for patients with a positive stool test. Our gastroenterologists perform high-quality colonoscopy and offer advanced endoscopic options for patients with complicated adenomas.
For patients who need surgical care for colorectal cancer, U.S. News & World Report rates colon cancer surgery at UVa as “high performing” – the best possible rating. To learn more about colorectal cancer screening and treatment options at UVa, visit uvahealth.com/services/colon-health.
Dr. Esteban Figueroa is a gastroenterologist at UVa Health.
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Genetic testing scams are rapidly becoming one of the top major fraud schemes across the country.
Medicare beneficiaries are being targeted by unscrupulous telemarketers, door-to-door salesmen, and seemingly helpful people manning the booth at a local health fair who claim that Medicare will pay for it and the test will be free. Don’t fall for it and certainly don’t hand over your Medicare card or agree to pay if the test is not prescribed by your doctor. Remember, if it sounds too good to be true, it probably is.
EXAMPLES OF GENETIC TESTING FRAUD
•A company or individual offers you “free” or “at no cost to you” testing without a treating physician’s order. The company then bills Medicare (usually thousands of dollars) for a broad range of genetic tests that you did not request or possibly even receive.
•A company or individual uses “telemedicine” to offer testing to you over the phone and arranges for an unrelated physician or “teledoc” to order the test.
•A company or individual sends you a kit for genetic testing and asks that you return the test with your Medicare number.
•A company or individual tries to bill Medicare for pharmacogenomic tests (to determine how you metabolize drugs) that are neither covered by Medicare or apply to you.
Here are just a few questions to ask when encountering potential genetic testing scams along with answers that provide information and guidance about how to handle each situation.
Q. Did the person/provider offer you a genetic test to screen for cancer or another condition?
A. Decline the offer. With so much interest in genetic tests as early warning systems for cancer, it makes sense that beneficiaries and others would wonder if Medicare covers genetic testing as a screening and prevention benefit. The answer, with one exception, is no. Although Medicare covers many genetic tests for diagnostic use, it only covers one genetic test to screen for cancer.
Since October 2014, Medicare Part B has paid for the Cologuard test, manufactured by Exact Sciences Corp of Madison, Wisconsin, to screen specifically for colorectal cancer. Scammers often refer to these tests as hereditary cancer screenings, DNA screenings, cancer screenings, genetic testing, pharmacological testing, Alzheimer’s screenings, dementia screenings, heart disease screenings, gene mutation screenings, genetic marker screenings, etc. Regardless of what the person calls it remember Medicare does not cover genetic tests to screen for cancer — except for one colorectal cancer DNA screening test from “Cologuard.”
Q. Did the person/provider say that Medicare covers genetic tests at no cost to you?
A. The tests are usually described as being available and useful for a wide range of people regardless of their health condition. Scammers will try to tell you that a person’s insurance will cover the tests for “free.” They make this claim because Medicare pays for diagnostic lab tests according to a fee schedule, with no deductible or coinsurance costs for patients, but only when medically necessary. The tests are only medically necessary with a treating physician’s order. If Medicare denies the tests, you could be charged the entire amount, which could easily run $9,000 to $11,000.
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Q. Did the person/provider say that Medicare covers this as a preventative test?
A. As mentioned earlier, Medicare does not cover genetic tests to screen for cancer as a preventative benefit, with only one exception for a colorectal cancer DNA screening test.
Q. Did the person/provider tell you what they are doing the genetic test for or which cancers they are testing for?
A. Medicare does not cover genetic tests for beneficiaries who do not have any symptoms or diagnoses of cancer. Medicare rules specifically state the following:n “Tests for screening purposes that are performed in the absence of signs, symptoms, complaints, or personal history of disease or injury are not covered as explicitly authorized by statute.”
Q. Did the person/provider tell you who would be following up with you regarding the results? Did the provider read your results and, if needed, use them to set up a treatment plan?
A. Lab tests like this must be ordered by a treating physician. Medicare rules state:
“All diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests must be ordered by the physician who is treating the beneficiary, that is, the physician who furnishes a consultation or treats a beneficiary for a specific medical problem and who uses the results in the management of the beneficiary’s specific medical problem. Tests not ordered by the physician who is treating the beneficiary are not reasonable and necessary.”
Q. Did the person/provider use scare tactics such as “your prescriptions could kill you” or “to prevent cancer,” claiming cancer and using the wrong prescription as the biggest killers of seniors?
A. If you have concerns about how your body is metabolizing your prescriptions or if you are at risk for cancer, you should talk with your health care provider, who should be aware of the prescriptions that you are on and your family’s medical history.
Your Pennsylvania Senior Medicare Patrol (SMP) is ready to provide you with the information you need to PROTECT yourself from Medicare fraud, errors, and abuse; DETECT potential fraud, errors, and abuse; and REPORT your concerns. SMPs and their trained volunteers help educate and empower Medicare beneficiaries in the fight against health care fraud. Your SMP can help you with your questions, concerns, or complaints about potential fraud and abuse issues. To receive local services in Pennsylvania visit or call (800) 356-3606.
(Joel Mekler is a certified senior adviser. Send him your Medicare questions at [email protected].)