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26-03-2013 | Oncology | Article

Circulating tumor DNA effective biomarker in breast cancer

Abstract

Free abstract

medwireNews: Circulating tumor DNA seems to be an effective biomarker for monitoring metastatic breast cancer, say researchers.

In a proof-of-concept analysis, circulating tumor DNA was an informative, inherently specific, and highly sensitive biomarker for the condition, report Nitzan Rosenfeld (University of Cambridge, UK) and colleagues.

Biomarkers that provide highly sensitive and specific measures of tumor burden are urgently needed as the serial imaging which is currently used often does not detect changes in tumor burden, explains the team.

For the study, the researchers compared the use of circulating tumor DNA with other circulating biomarkers (CA 15-3 and circulating tumor cells) and computed tomography (CT) in patients who were receiving systemic treatment for metastatic breast cancer.

Using either targeted or whole-genome sequencing, the team identified somatic genomic alterations in 30 of 52 patients. In these women, they then measured levels of the circulating biomarkers present in plasma specimens, which they had collected serially over a 1-year period.

Among the 30 women, circulating tumor DNA was detected in 29 (97%), while CA 15-3 was detected in 21 of 27 (78%), and circulating tumor cells in 26 of 30 (87%), respectively.

Further analysis showed that circulating tumor DNA had a significantly improved sensitivity compared with CA 15-3 and circulating tumor cells, at 85% versus 59%, and 90% versus 67%, respectively.

As reported in the New England Journal of Medicine, the researchers then compared the performance of the circulating biomarkers and CT in 20 patients with measurable disease.

Circulating tumor DNA was detected and showed serial changes in 19 (95%) of 20 women, with changing levels that correlated with treatment responses seen on imaging.

Similar findings were observed for women with five or more circulating tumor cells per 7.5 mL of blood (10 of 20 [50%] of patients). However, in the remaining 10 women who had fewer than five cells per 7.5 mL of blood, the number of circulating tumor cells was uninformative.

Similarly, among women with high levels of CA 15-3, fluctuating levels of the biomarker corresponded with treatment response on imaging, but in those with levels of 50 U or less per mL (eight of 19 patients [42%]), no consistent serial changes in CA 15-3 levels were seen.

"In the detection of metastatic breast cancer, circulating tumor DNA shows superior sensitivity to that of other circulating biomarkers and has a greater dynamic range that correlates with changes in tumor burden," conclude the researchers.

They add: "Circulating tumor DNA represents a "liquid biopsy" alternative, allowing for sensitive and specific serial sampling to be performed during the course of treatment."

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Sally Robertson, medwireNews Reporter

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