In a new study, Biodesign teams up with the Translational Genomics Research Institute (TGen) and the Mayo Clinic in Arizona present a blood-based cancer monitoring test known as TARDIS, which improves the sensitivity of such tests by 100 times or more.
A new type of blood test for breast cancer could help avoid thousands of unnecessary surgeries and otherwise precisely monitor disease progression, according to a study led by the Translational Genomics Research Institute (TGen), Mayo Clinic in Arizona and the Biodesign Institute at Arizona State University.
TGen is an affiliate of City of Hope, which along with Cambridge University also contributed to this study.
Published today in the premier journal Science Translational Medicine, the study suggests that the test called TARDIS — TARgeted DIgital Sequencing — is as much as 100 times more sensitive than other blood-based cancer monitoring tests.
TARDIS is a “liquid biopsy” that specifically identifies and quantifies small fragments of cancer DNA circulating in the patient’s bloodstream, known as circulating tumor DNA (ctDNA). According to the study, TARDIS detected ctDNA in as low as 2 parts per 100,000 in patient blood.
“By precisely measuring ctDNA, this test can detect the presence of residual cancer, and inform physicians if cancer has been successfully eradicated by treatment,” said Muhammed Murtaza, M.B.B.S., Ph.D., Assistant Professor and Co-Director of TGen’s Center for Noninvasive Diagnostics. He also holds a joint appointment on the Research Faculty at Mayo Clinic Arizona, and is one of the study’s senior authors.
“This data represents an exciting strategy to improve the sensitivities of liquid biopsies, which have been challenging for breast cancer,” said Karen Anderson, M.D., Ph.D., a researcher at the Biodesign Institute, a medical oncologist at Mayo Clinic Arizona, and one of the study’s contributing authors. “This work represents highly collaborative efforts across multiple institutions, and with the generosity and foresight of our patients who have contributed to this study.”
Anderson actively recruits patients and conducts clinical cancer trials. Her focus areas include postoperative therapies to reduce breast cancer relapse risk; treatments for metastatic breast cancer, especially targeted therapies and immunotherapies; genomic factors that may guide treatment decisions in breast cancer, new diagnostics for early detection for a broad range of cancer indications and new vaccines for cancers.
As Dr. Murtaza explained, TARDIS is precise enough to tell if early stage breast cancer patients have responded well to pre-operative drug therapy. It is more sensitive than the current method of determining response to drug therapy using imaging.
“This has enormous implications for women with breast cancer. This test could help plan the timing and extent of surgical resection and radiation therapy after patients have received pre-operative therapy,” said Dr. Barbara A. Pockaj, M.D., a surgical oncologist who specializes in breast and melanoma cancer patients at Mayo Clinic in Arizona, and is the study’s other senior author. Dr. Pockaj is the Michael M. Eisenberg professor of surgery and the chair of the Breast Cancer Interest Group (BIG), a collaboration between researchers at Mayo, TGen and ASU.
Unlike traditional biopsies, which only produce results from one place at one time, liquid biopsies use a simple blood draw, and so could safely be performed repeatedly, as often as needed, to detect a patient’s disease status.
This study was performed in collaboration with Carlos Caldas, M.D., Professor of Cancer Medicine at the University of Cambridge and Director of the Breast Cancer Programme at Cambridge Cancer Centre.
“TARDIS is a game changer for response monitoring and residual disease detection in early breast cancer treated with curative intent. The sensitivity and specificity of patient-specific TARDIS panels will allow us to tell very early, probably after one cycle, whether neo-adjuvant (before surgery) therapy is working and will also enable detecting micro-metastatic disease and risk-adapted treatment after completing neo-adjuvant therapy,” said Dr. Caldas, who also is Senior Group Leader at CRUK Cambridge Institute, and one of the study’s contributing authors.
Following further clinical testing and trials, TARDIS could someday be routinely used for monitoring patients during cancer treatment, and discovering when patients are essentially cured and cancer free.
“The results of these tests could be used to individualize cancer therapy avoiding overtreatment in some cases and under treatment in others,” Dr. Murtaza said. “The central premise of our research is whether we can develop a blood test that can tell patients who have been completely cured apart from patients who have residual disease. We wondered whether we can see clearance of ctDNA from blood in patients who respond well to pre-surgical treatment.”
Current tests and imaging lack the sensitivity needed to make this determination.
“Fragments of ctDNA shed into blood by tumors carry the same cancer-specific mutations as the tumor cells, giving us a way to measure the tumor,” said Bradon McDonald, a computational scientist in Dr. Murtaza’s lab, and the study’s first author.
“The problem is that ctDNA levels can be so low in non-metastatic cancer patients, there are often just not enough fragments of ctDNA in a single blood sample to reliably detect any one mutation. This is especially true in the residual disease setting, when there is no obvious tumor left during or after treatment,” McDonald said. “So, instead of focusing on a single mutation from every patient, we decided to integrate the results of dozens of mutations from each patient.”
The study results suggest that tumor-guided personalized ctDNA analysis, using TARDIS, is a promising approach to identifying patients with pathological complete response following pre-surgical drug therapy.
“Together with imaging and tissue-based predictive biomarkers, ctDNA could become a useful diagnostic test to determine individualized decisions about additional treatment,” Dr. Murtaza said.
Dr. Pockaj affirmed: “We are excited that TARDIS has the potential to really individualize clinical management of patients with non-metastatic cancer.”
Thomas Slavin, M.D., Assistant Clinical Professor at City of Hope National Medical Center, and a contributing author of the study, noted that “reliably identifying, often multiple, circulating tumor mutations in the plasma of patients with non-metastatic breast cancer also holds promise that ctDNA may one day be a great tool for early breast cancer detection.”
TGen is now focused on evaluating the best partners to work with to automate and scale TARDIS, so it can be made available broadly to benefit patients in need.
Patient samples for this study were collected at Mayo Clinic, at Addenbrookes Hospital at the University of Cambridge, and at City of Hope.
This research was funded by: the National Cancer Institute, Mayo Clinic Center for Individualized Medicine, the V Foundation for Cancer Research, Science Foundation Arizona, The Ben and Catherine Ivy Foundation, SmartPractice, City of Hope and TGen.
About TGen, an affiliate of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
About the Biodesign Institute at Arizona State University
The Biodesign Institute at Arizona State University works to improve human health and quality of life through its translational research mission in health care, energy and the environment, global health and national security. Grounded on the premise that scientists can best solve complex problems by emulating nature, Biodesign serves as an innovation hub that fuses previously separate areas of knowledge to serve as a model for 21st century academic research. By fusing bioscience/biotechnology, nanoscale engineering and advanced computing, Biodesign’s research scientists and students take an entrepreneurial team approach to accelerating discoveries to market. They also educate future generations of scientists by providing hands-on laboratory research training in state-of-the-art facilities for ASU students.
Biodesign researcher Karen Anderson, working in conjunction with Joshua LaBaer, executive director of the Biodesign Institute and director the Biodesign Center for Personalized Diagnostics, helped develop a first-of-its-kind blood-based test for detecting breast cancer that reduces false positives and provides a diagnostic tool to complement breast imaging, especially in dense breast tissue situations. The technology was licensed to Provista Diagnostics and used in their Videssa Breast product in 2017.
Media Contact:
Steve Yozwiak TGen Senior Science Writer 602-343-8704 syozwiak@tgen.org