A blood test that tracks fragments of DNA shed by dying tumor cells could be used to monitor how well patients are responding to cancer treatment.
In women with advanced breast cancer, the blood test could provide a noninvasive alternative to biopsies, and help adapt treatment to individual patients and the progress of disease.
A team of scientists at the Cancer Research Institute (Cambridge, UK) compared circulating tumor DNA against the two other well-known biomarkers, cancer antigen 15-3 (CA 15-3), and circulating tumor cells, to assess disease progress in 30 women being treated for advanced metastatic breast cancer. Serial blood samples were collected between April 2010 and April 2012 at intervals of three or more weeks.
Sequencing was performed on DNA from breast cancer specimens and matched normal tissue specimens, with the use of one or both of two methods: tagged-amplicon deep sequencing for the gene encoding the phosphatidylinositol- 4,5-bisphosphate 3-kinase, catalytic subunit alpha protein (PIK3CA) and for the gene encoding for tumor protein p53 (TP53) or paired-end whole-genome sequencing. The scientists measured the levels of CA 15-3 in 50 μL aliquots of plasma by means of the ADVIA Centaur immunoassay system (Siemens Healthcare; Erlangen, Germany).
The team compared the three sets of biomarker results with computed tomography (CT) scans to see if changes in the biomarkers matched up with changes in the cancer. They found that out of the three biomarkers the circulating tumor DNA gave the most accurate real time picture of changes taking place in the body. They successfully detected tumor DNA in 29 of the 30 women (97%), while circulating tumor cells were detected in 26 of the 30 (87%) and CA 15-3 was detected in 21 of 27 (78%).
Carlos Caldas, MD, FMedSci, co-lead author said, “We can use blood samples to track how breast cancer is progressing as fragments of DNA are shed by cancer cells when they die, meaning they can be detected in blood samples using sensitive new sequencing techniques. The levels of tumor DNA are telling us how the cancer is responding to treatment.” Circulating tumor DNA represents a “liquid biopsy” alternative, allowing sensitive and specific serial sampling to be performed during the course of treatment. The study was published on March 13, 2013, in the journal New England Journal of Medicine (NEJM).