COLUMBUS, OHIO - A clinically relevant "liquid biopsy" test can be used to profile cancer genomes from blood and predict survival outcomes for patients with metastatic triple negative breast cancer (TNBC), according to new research published by a multi-institutional team of researchers with The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard.
Although TNBC represents just 10-15 percent of all breast cancer diagnoses, the disease is responsible for 35 percent of all breast cancer-related deaths. While significant advances in understanding the genomic drivers of primary TNBC have been made in the past decade, relatively little is known about metastatic disease because surgical tumor biopsies are rarely obtained from these patients.
For this new study, researchers completed what is believed to be the largest genomic characterization of metastatic TNBC derived exclusively from liquid biopsies. This was done by measuring cell-free DNA levels in the blood -- DNA that is excreted from both cancerous and normal cells into the bloodstream. The study included blood samples from 164 women with metastatic TNBC.
"Traditionally, we would need to obtain a tissue biopsy to perform the whole genome sequencing tests that could reveal potential DNA-level mutations driving a patient's specific cancer. For metastatic breast cancer patients, however, tissue biopsy can be risky or painful," says Daniel Stover, MD, co-first and co-corresponding author of the study and a breast medical oncologist/researcher with the OSUCCC - James. "Being able to do this type of genomic analysis from a simple blood draw allows us to get a picture of a patient's specific cancer genomic characteristics in a less invasive way."
Researchers then used a customized liquid biopsy technique they developed to distinguish levels of DNA from cancer cells and healthy cells (tumor fraction). Whole genome sequencing was performed to identify potential mutations associated with metastatic TNBC.
The team found that 64 percent of patients had more than 10 percent tumor DNA, and that this threshold of tumor DNA was correlated with poor survival outcomes in patients with metastatic TNBC. Additionally, researchers used genome-wide data to identify specific abnormal genes more frequently altered in metastatic TNBC compared with primary cases of the disease. These abnormal genes were associated with survival outcomes in the metastatic TNBC patient population and could serve as targets for new therapies for at-risk populations in the future, researchers say.
"The recognition that a significant fraction of patients harbor greater than 10 percent tumor DNA in blood suggests that liquid biopsies may enable routine and non-invasive profiling of cancer genomes for patients with metastatic TNBC," says Viktor Adalsteinsson, PhD, co-corresponding author and group leader of the Blood Biopsy Team at the Broad Institute.
Researchers say this study suggests that minimally invasive liquid biopsies could be used as a new predictive marker for metastatic TNBC.
"This is a very challenging disease. Our team's findings -- and others enabled by liquid biopsy --could improve how we track disease and treat our patients in the clinic," says Heather Parsons, MD, MPH, co-first author of the study and breast medical oncologist/researcher at Dana-Farber Cancer Institute and Harvard Medical School.
"These are exciting and important discoveries that could help us understand how a patient's cancer is likely to progress and, ultimately, could have the potential to guide treatment decisions based on specific genomic risk factors," adds Stover, whose plans for his laboratory at the OSUCCC - James include expanded validation studies with a goal to bring this test into the clinic and investigate new methods to study circulating DNA.
These findings will appear in the February 20, 2018, print issue of the Journal of Clinical Oncology. Stover conducted this research while serving as an instructor of medicine at the Dana-Farber Cancer Institute in Boston, in collaboration with the Blood Biopsy Team at the Broad Institute and the Breast Oncology Group at the Dana-Farber Cancer Institute.
Collaborators in this study include Gavin Ha, William Barry, Hao Guo, Atish Choudhury, Melissa Hughes, Deborah Dillon, Ann Partridge, Nikhil Wagle, Ian Krop, Eric Winer, Sara Tolaney and Nancy Lin of the Dana-Farber Cancer Institute; J. Christopher Love of the Massachusetts Institute of Technology; and Samuel Freeman, Gregory Gydush, Sarah Reed, Gad Getz and Todd Golub of the Broad Institute.
Funding was provided by the Gerstner Family Foundation, Susan G. Komen for the Cure, The Pink Agenda, Breast Cancer Research Foundation, V Foundation for Cancer Research and National Cancer Institute.
Additional clinical research on liquid biopsy is underway with current TNBC patients at the OSUCCC - James and Dana-Farber Cancer Institute. To learn more about breast cancer treatment and research at the OSUCCC - James, visit cancer.osu.edu/breastcancer.
About the OSUCCC - James
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of 49 National Cancer Institute-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet ® designation, the highest honor an organization can receive for quality patient care and professional nursing practice. With 21 floors and more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, visit cancer.osu.edu.
About Dana-Farber Cancer Institute
From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world's leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report's Best Hospitals for both adult and pediatric cancer care.
Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement and advocacy. Dana-Farber/Brigham and Women's Cancer Center provides the latest in cancer care for adults; Dana-Farber/Boston Children's Cancer and Blood Disorders Center for children. The Dana-Farber/Harvard Cancer Center unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care provides high quality cancer treatment in communities outside Boston's Longwood Medical Area.
Dana-Farber is dedicated to a unique 50/50 balance between cancer research and care, and much of the Institute's work is dedicated to translating the results of its discovery into new treatments for patients in Boston, and around the world.
About the Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods, and data openly to the entire scientific community.
Founded by MIT, Harvard, Harvard-affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff, and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.