New Molecular Test to Monitor Breast Cancer Recurrence by Sequencing Circulating Tumor Cells

Wayne Kuznar

April 2014, Vol 5, No 3 - Personalized Medicine


A genomic test to sequence the circulating tumor cells (CTCs) from whole blood, ClearID Breast Cancer from Cynvenio Biosystems, is now available commercially to molecularly monitor for breast cancer recurrence. The test uses a standard blood draw from which DNA from tumor cells is isolated and interrogated using next-generation–sequencing tools to determine the presence of cancer-associated DNA mutations.

The Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory at Cynvenio has a validated protocol to recover CTCs and evaluate them for the presence of more than 4500 single-point genetic mutations.

According to André de Fusco, Chief Executive Officer and Director of Cynvenio, the ClearID test is useful for patients with breast cancer who are at high risk for disease recurrence after treatment, because CTCs reflect the underlying biology of the disease process. “It is a great way to detect the metastatic process because that’s what these tumor cells in blood are responsible for,” Mr de Fusco said.

The ClearID test evaluates blood samples for elevated numbers of cells that are phenotypically characterized as CTCs. When elevated, the CTCs are examined for the presence of somatic mutations that are not found in the germline sequence. “These data can provide additional insight into the molecular character of disease, and do so with a very stringent analytical specificity due to the multiple biomarkers involved in the test and the evaluation of the CTC genome for somatic mutations,” according to the company.

Physicians who send in a blood sample using the patient sample kit receive a comprehensive report of actionable genomic alterations plus associated treatments for each alteration found. The fixed sample is stable for 96 hours without refrigeration. This platform to enumerate and isolate CTCs has been patented.

The test, which can identify mutations present in as few as 1% of CTCs, is designed to be a “blood to readout” solution, with reports available in 3 to 10 days, said Mr de Fusco. It offers the opportunity for longitudinal monitoring to track the disease course.

“We’re going to give doctors an ability with the same blood draw to also monitor estrogen receptor status, progesterone receptor status, as well as human epidermal growth factor receptor 2,” Mr de Fusco said. “In one single test, they’ll have pretty much everything they need to look at breast cancer. In the metastatic patient, they’re going to be interested in estrogen receptor and progesterone receptor status, but they may also want to know if there’s a PIK3CA mutation in an unresponsive patient in the third line of therapy.”

The advanced genomic reporting contains not only the cancer-associated mutations identified but also the targeted treatments—both those approved by the US Food and Drug Administration and those currently in clinical trials—to which the mutation is sensitive, as well as advice on off-label treatments. “The doctor doesn’t have to be a genetic oncologist to know what to do,” said Mr de Fusco.