Circulating cell-free DNA is better at detecting changes in tumor burden in women undergoing treatment for metastatic breast cancer than other blood-based markers. Circulating cell-free DNA (also called circulating tumor DNA) had higher sensitivity and a greater dynamic range than either circulating tumor cells (CTCs) and cancer antigen 15-3 (CA 15-3), according to a study published in the March 28 issue of the New England Journal of Medicine. The researchers recruited women undergoing active treatment for metastatic breast cancer. Serial blood samples were collected at intervals of three or more weeks. Circulating cell-free DNA improved sensitivity compared to CA 15-3 by 26 percent (85 percent versus 59 percent, respectively). Similarly, a 27 percent improvement in sensitivity was seen using circulating tumor DNA compared to CTCs (90 percent versus 67 percent). CTCs were quantified using the U.S. Food and Drug Administration-approved CellSearch test by Veridex. There were 133 times the number of amplifiable copies of circulating tumor DNA as CTCs when comparing the medians. As might be expected, increasing levels of both circulating cell-free DNA and CTCs were associated with significantly inferior overall survival, but cell free-DNA provided the earliest measure of treatment response in 10 of 19 women (53 percent). […]
Circulating cell-free DNA is better at detecting changes in tumor burden in women undergoing treatment for metastatic breast cancer than other blood-based markers. Circulating cell-free DNA (also called circulating tumor DNA) had higher sensitivity and a greater dynamic range than either circulating tumor cells (CTCs) and cancer antigen 15-3 (CA 15-3), according to a study published in the March 28 issue of the New England Journal of Medicine.
The researchers recruited women undergoing active treatment for metastatic breast cancer. Serial blood samples were collected at intervals of three or more weeks. Circulating cell-free DNA improved sensitivity compared to CA 15-3 by 26 percent (85 percent versus 59 percent, respectively). Similarly, a 27 percent improvement in sensitivity was seen using circulating tumor DNA compared to CTCs (90 percent versus 67 percent). CTCs were quantified using the U.S. Food and Drug Administration-approved CellSearch test by Veridex. There were 133 times the number of amplifiable copies of circulating tumor DNA as CTCs when comparing the medians. As might be expected, increasing levels of both circulating cell-free DNA and CTCs were associated with significantly inferior overall survival, but cell free-DNA provided the earliest measure of treatment response in 10 of 19 women (53 percent).
“This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer,” write the authors, led by Sarah-Jane Dawson, Ph.D., from University of Cambridge in the United Kingdom.
In an accompanying editorial, Marc Lippman, M.D., from University of Miami, and C. Kent Osborne, M.D., from the Baylor College of Medicine in Houston, caution that unlike other cancers with more homogenous or common mutations, breast cancer (as witnessed by the fact that mutations or structural variants could only be identified in the blood of 30 of the initial 52 patients) would require “substantially deep sequencing” thus making a universal panel unlikely to work. Personalized panels would be costly and rate-limiting. Additionally, they say, more research is needed both in determining if analyzing circulating tumor DNA improves patient outcomes and if the strategy is cost-effective.
