Automated Liquid Biopsy Test Detects Advanced Breast Cancer in Five Hours

By LabMedica International staff writers
Posted on 24 Jun 2022

Image: Automated liquid biopsy test quickly IDs cancer DNA in patients with metastatic breast cancer (Photo courtesy of Johns Hopkins)

Many patients with breast cancer do not respond to chemotherapy but go through multiple cycles of treatment before oncology teams can perform imaging studies to determine if a treatment is effective. Imaging can be effective at detecting changes in larger tumors, but it is nearly impossible to identify changes in smaller tumors. Now, a novel, automated liquid biopsy test in development can accurately detect the presence of cancer DNA in the blood of patients with metastatic breast cancer within five hours. The test, currently a prototype for research use only, potentially could be used to quickly help oncologists determine if cancer treatments are working.

The test, called the Liquid Biopsy for Breast Cancer Methylation (LBx-BCM), has been developed by researchers at Johns Hopkins Medicine (Baltimore, MD, USA) and is compatible with the GeneXpert molecular testing platform from Cepheid (Sunnyvale, CA, USA). It can detect methylation, a type of chemical tag, in one or more of nine genes altered in breast cancers in 4.5 hours. The test requires less than 15 minutes of hands-on time by a laboratory technician.

With the LBx-BCM test, a technician can place blood or plasma samples from cancer patients in tubes containing a reagent, a mixture used for extracting DNA, and place the contents in cartridges for the commercial system to chemically modify the DNA, and then amplify and detect methylated genes, returning results quickly. The assay looks for methylation markers (chemical alterations to DNA particular to cancer cells) among a panel of nine genes that recognize the four subtypes of breast cancer. The genes are AKR1B1, TM6SF1, ZNF671, TMEFF2, COL6A2, HIST1H3C, RASGRF2, HOXB4 and RASSF1.

To test LBx-BCM, investigators first had two individuals run the test on separate days, using stored samples from 11 patients with metastatic breast cancer and four without breast cancer. Results were the same for more than 90% of the cases. They also studied the test’s ability to detect metastatic breast cancer in two sets of samples from previous studies at Johns Hopkins. They examined cumulative methylation of the nine genes in 20 serum samples from patients with metastatic breast cancer and 20 from people without breast cancer.

A second set of samples from 40 people with metastatic breast cancer, 17 with benign breast disease and nine without breast cancer, was analyzed. In both sets, LBx-BCM detected two- to 200-fold more methylated DNA in plasma samples from those with breast cancer than in normal or benign samples. The test was found to correctly detect cancer 83% of the time, and correctly rule out cancer 92% of the time, for an overall diagnostic accuracy of 85%.

“Our goal was to develop an assay that would be sophisticated yet simple to perform worldwide and could be used at the point of care to provide same-day feedback to clinicians and patients,” said senior study author Saraswati Sukumar, Ph.D., professor of oncology and pathology at the Johns Hopkins University School of Medicine. “If we are able to show by this cartridge assay that we are indeed successful in predicting the course of treatment, we might be able to institute changes in the way we look at chemotherapy and the way we treat patients for metastatic breast cancer.”

Related Links:
Johns Hopkins Medicine
Cepheid