Circulating breast cancer DNA a clear indication of malignancy

While radiographic evaluation of breast cancer may provide important information about tumor structures, it does not provide information about tumor burden. A novel method of cancer assay singling out circulating tumor DNA could provide additional information about tumor activity and lead to more accurate assessment and patient prognosis, according to a study published in the March edition of the New England Journal of Medicine.

Sarah-Jane Dawson, PhD, from the department of oncology at the University of Cambridge and Cancer Research UK Cambridge Institute in Cambridge, U.K., and colleagues, compared CT imaging studies of tumors with assays of circulating tumor DNA, the cancer antigen known as CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer.

“Treatment response is generally assessed with the use of serial imaging, but radiographic measurements often fail to detect changes in tumor burden,” wrote Dawson et al. “Therefore, there is an urgent need for biomarkers that measure tumor burden with high sensitivity and specificity.”

The prospective, single-center study compared the sensitivity of circulating tumor DNA, CA 15-3, and circulating tumor cell measurement to conventional medical imaging, in 30 women being treated for metastatic breast cancer. Serial blood samples were taken at intervals of three or more weeks between April 2010 and April 2012. The researchers used targeted or whole-genome sequencing and identified somatic genomic alterations and created custom assays to extrapolate quantitative data about circulating tumor DNA in multiple plasma samples while at the same time collecting data about CA 15-3 levels and amounts of circulating tumor cells. Blinded CT imaging studies were completed for all subjects.

Results of the study indicated that circulating levels of tumor DNA was a better predictor of tumor burden than both CA 15-3 and circulating tumor cells and provided functional information that anatomic CT imaging could not.

“This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer,” the researchers added.

In 29 of the 30 patients, circulating tumor DNA was detected using personalized assay identifying somatic genomic alterations. Circulating tumor cells were found in 26 out of 30 women and CA 15-3 was present in 21 of 27 women.

“Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells,” explained the authors. “Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53 percent).”