Detecting tumor DNA in breast cancer patients with high sensitivity!

Detecting tumor DNA in breast cancer patients with high sensitivity!


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 new study.

Published in the 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 one of the study's senior authors.
For example, the author 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. The authors were able to accurately detect circulating tumor DNA (ctDNA) and signs of residual disease in 33 women with breast cancer.

"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 the study's other senior author.

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.

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.
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 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," said the lead. "So, instead of focusing on a single mutation from every patient, we decided to integrate the results of dozens of mutations from each patient."

Their assay analyzes an amount of DNA equivalent to a single tube of blood and can simultaneously study eight to 16 known mutations. TARDIS successfully detected ctDNA in plasma samples from 33 patients with breast cancer before they started treatment, and revealed the patients had lower concentrations of ctDNA after treatment was completed. Furthermore, patients who responded the best to chemotherapy displayed a 96% decrease in ctDNA abundance, while patients with residual disease showed a 77% decrease - indicating the platform could guide the personalized management of patients at risk of cancer recurrence.

The study results suggest that personalized ctDNA analysis, using TARDIS, is a promising approach to identifying patients with a curative response following pre-surgical drug therapy.

"Together with imaging and tissue-based predictive biomarkers, ctDNA is rapidly becoming a useful diagnostic test to determine individualized decisions about additional treatment," the senior author said.


https://www.tgen.org/news/2019/august/07/new-ctdna-blood-test-for-cancer/

https://stm.sciencemag.org/content/11/504/eaax7392
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fpersonalized&filter=22

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