Intermountain Healthcare Researchers Launch Major Three-Year Genomics Breast Cancer Study

Cancer researchers at Intermountain Medical Center and the Intermountain Healthcare Precision Genomics Program in Salt Lake City are launching a three-year study to determine if a blood test that looks for DNA from a cancer tumor can be used to complement mammography to improve the way breast cancer is diagnosed.

The goal of this new genomics study is to show whether screening patients for the presence of circulating tumor DNA, known as ctDNA, can successfully detect breast cancer using a blood draw.

Breast cancer is the second-leading cause of cancer deaths in women, behind only lung cancer, with an estimated 40,610 deaths each year from the disease. Nearly 253,000 new cases of invasive breast cancer are diagnosed each year, along with about 60,000 non-invasive, early-stage cases, according to the American Cancer Society.

The Intermountain study is unique in that researchers will also help develop a specific test to check for ctDNA, and will have access to both mammography results and the DNA blood test results, which will allow a direct comparison of the “liquid-based biopsy” to be made.

The idea behind the science is simple, though researchers say the execution is not yet proven: Little pieces of DNA that come from dying cells end up in the peripheral blood stream, including circulating tumor cells. The goal of researchers is to use those markers to identify breast cancer, perhaps even before mammography can detect it, said Lincoln Nadauld, MD, PhD, co-lead investigator of the study and executive director of the Intermountain Healthcare Precision Genomics Program.

“As a tumor is growing, some of the cells will die and their DNA will end up in the peripheral blood stream,” Dr. Nadauld said. “We’re able to distinguish DNA from cancer vs. DNA from normal cells. The idea is to leverage DNA to see if we can detect that it comes from a tumor.”

In the study, patients with known breast cancer will be compared with those in a screening group.

“We don’t know what we’ll see yet,” said Brett Parkinson, MD, co-lead investigator of the study, who is also imaging director and medical director of the Intermountain Medical Center Breast Care Center in Murray. “We might find those who have breast cancer will have a negative blood test and learn it’s not a good screening tool.”

Even a successful blood test isn’t expected to replace mammography outright. If it detects the circulating tumor DNA, imaging would be needed to find the tumor. But it could help eliminate unneeded biopsies, Dr. Parkinson added.

Dr. Nadauld said cancers have mutations in their DNA that aren’t always unique.

“Sometimes those are the same whether it’s a breast cancer or a colon cancer. If we do create a blood test, it’s possible it would detect mutant DNA, but it might look so similar it would be hard to tell what kind of cancer it came from,” he said. “That’s part of what this trial is going to accomplish. We want to determine the signature for early breast cancer.”

If successful, a liquid biopsy might also be used to monitor a breast cancer survivor for recurrence, Dr. Nadauld said. It might even lead to development of similar tests for different types of cancer. But that would be a challenge for the future.

“We want to approach this with laser-like focus,” he said. “It’s needed to help us diagnose breast cancer. We need to detect it earlier, when it’s curable.”

Breast cancer survival depends largely on finding the disease early —and mammography is the only screening exam that’s been shown by multiple randomized clinical trials to reduce the mortality rate for breast cancer. Since 1991, the death rate from breast cancer is down 38 percent, largely because mammography screening tests lead to early detection.

Although mammography finds most breast cancers, it may not detect malignancy in women who have dense breast tissue, especially premenopausal women, or those under 50.

“We pick up most breast cancer in women with average breast density,” said Dr. Parkinson. “When breast tissue is denser, we can miss up to 30 percent of breast cancers.”

Mammography also has a false-positive or call-back rate of 10 percent, which may subject women to additional imaging and emotional duress. Plus, a mammogram can be uncomfortable, since breast tissue is compressed for imaging, which also exposes a woman to a small amount of radiation. Mammography may also be inconvenient, often requiring women to take time off work, he noted.

For those, and perhaps other reasons, mammography screening rates in the United States are low. In Utah, only about 65 percent of eligible women are screened, despite Intermountain Healthcare’s recommendations that women over 40 undergo yearly screening mammography. All major medical and advocacy organizations agree that screening every year after a woman is 40 saves more lives. About 20 percent of breast cancers occur in women under 50.

Dr. Nadauld said the unusual confluence of three factors weigh in Intermountain’s favor on this quest, starting with access to a lot of patients in one place who are getting mammograms, which are the gold standard screening test for breast cancer. Second, the researchers have access to the results of those mammograms; they know if the results were positive or negative. The third major factor is Intermountain’s genomic technology capability.

“This is the big conversation right now in all of oncology — the use of liquid biopsy to determine how to screen for breast cancer, a woman’s risk of recurrence, and how to monitor their treatment,” Dr. Nadauld said.

The study is being made possible by a generous donation from the Beesley Family Foundation.

New Technology Aims to turn Complicated Lab Tests into Point-of-Care Tests for First Responders

Carbon monoxide (CO) poisoning can have tragic consequences if victims are not rescued or treated. First responders at the scene may not know immediately if a conscious patient is a victim of CO poisoning.

Normally, these type of tests are taken with an arterial blood sample (typically an artery in the arm), and are then sent off to a central lab, where a bench top unit uses spectroscopy and electrochemical sensor measurements to provide results.  It can take hours to get the results.

But what if a lab in a hospital is not an option and time may be ticking for first responders at a scene of a possible CO poisoning?

Rapid Response

Toronto-based ChroMedx, a medical technology company focused on the development of novel medical devices for in vitro diagnostics and point-of-care testing is working to address this. Their flagship device, the HemoPalm utilizes a small sample of blood via the finger, providing a result on the spot, with no specialist required. Central to the HemoPalm, is its ability to fully integrate CO-oximetry, measured through spectroscopy (the only method for CO-oximetry) which allows the user to measure total hemoglobin (Hb), Oxy-Hb, Deoxy-Hb, Met-Hb and carboxy-Hb, simultaneously with blood gases and electrolytes measured with electrochemical sensors.

The technology is especially beneficial to first responders, who can take the blood sample right at the scene and have the data available upon arrival to the hospital before the patient even arrives into the ER. The information can also be transmitted back to the hospital before the patient is wheeled into the ER triage.

Hospital Setting

In a hospital setting, the HemoPalm could simplifying sample collection and expediting patient results, both in the emergency department and the operating room, where the device could replace multiple machines currently in use. Another use would be for respiratory care, allowing respiratory therapists and visiting nurses to optimize treatment in the hospital and at home with comprehensive results of oxygen in the blood.

A second cartridge, the HemoPalm B, is being developed to measure bilirubin (which may be used to monitor liver function).  Bilirubin in high levels is an indication of jaundice, a potentially dangerous condition for newborns of which approximately 15% will develop this condition.  The heel-prick method of sampling, as provided by the HemoPalm system, makes sample collection easy with minimal trauma to the baby and minimal blood loss.   Once diagnosed, treatment is relatively straightforward, and pre-discharge testing could predict virtually all cases of jaundice and ensure proper parental response and care.

Future Tests

Other cartridges planned for development include testing for lactate, which is an indication of sepsis (blood poisoning), a common and deadly condition in the Emergency Department; creatinine, a measure of kidney function; and beta-hydroxybutyrate, elevated in diabetic emergencies.

Wayne Maddever, ChroMedx’s CEO said he expects to see HemoPalm in studies for FDA approvals within a year.  For more information, log on to http://www.chromedx.com