A new blood test for tracking breast cancer in patients with early stage disease may enable physicians to more sensitively monitor patients, including looking at responses to treatment, tailoring treatments more effectively and preventing some invasive surgeries.
The research published today in Science Translational Medicine is a collaborative effort between the Translational Genomics Research Institute (TGen), an affiliate of City of Hope in California and the Mayo Clinic in Arizona and the Cancer Research UK Cambridge Institute.
The test called "TARDIS" (TArgeted DIgital Sequencing) has been suggested to be up to 100 times more sensitive than other existing blood-based cancer monitoring tests. It works by looking for tiny fragments of DNA which come from a patients tumor, but are found in the bloodstream called "circulating tumor DNA (ctDNA)," and has been described to pick up as little as 2 parts of ctDNA in 100,000.
“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, PhD, assistant professor and co-director of T-Gen's Center for Noninvasive Diagnostics and one of the study's senior authors.
Liquid biopsies are an extremely hot and occasionally controversial topic in the biotech world, but many of them have been developed to detect cancers in those with established, advanced disease.
“Until now, blood tests for breast cancer have only been sensitive enough to reliably identify tumor DNA in people with advanced disease. We’ve shown that TARDIS is able to detect circulating DNA at extremely low concentrations in the blood, opening up the possibility of monitoring patients with early-stage breast cancer to find out how their disease is responding to treatment” said Murtaza.
TARDIS is more precise than other cancer blood tests as it uses DNA sequencing data taken from a traditional needle biopsy of each individual patient's tumor and then uses computer algorithms to identify mutations likely to be present in all cancer cells and hence, ctDNA in the blood.
The study used blood samples from 33 breast cancer patients treated at either Addenbrookes Hospital in the U.K., the Mayo Clinic in Arizona or at City of Hope in California and looked for specific mutations known to be found in breast cancer. At diagnosis, TARDIS detected significant amounts of breast cancer DNA in all patients. 22 of these people were then treated with neoadjuvant chemotherapy, a first step of treatment for some patients to reduce the size of a tumor before surgical treatment.
Around a third of patients treated with neoadjuvant chemotherapy achieve a complete response to the therapy, meaning when they do have breast surgery, there is no visible evidence of the tumor in the removed breast tissue. In these people, TARDIS detected a far smaller amount of tumor ctDNA than in the two-thirds of people where tumor is still detectable in the breast tissue removed by surgery. Currently, doctors and surgeons have no way of reliably detecting who these 30% of people are who have responded so well to neoadjuvant chemotherapy that they may not need the invasive surgical procedure, but they hope that TARDIS may change this.