The management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment, and improved biomarkers are needed.
Biomarkers such as cancer antigen 15-3 ( CA 15-3 ) and circulating tumor cells have been widely studied. However, circulating cell-free DNA carrying tumor-specific alterations ( circulating tumor DNA ) has not been extensively investigated or compared with other circulating biomarkers in breast cancer.
Researchers compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy.
Investigators used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. CA 15-3 levels and numbers of circulating tumor cells were measured at identical time points.
Circulating tumor DNA was successfully detected in 29 of the 30 women ( 97% ) in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women ( 78% ) and 26 of 30 women ( 87% ), respectively.
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.
Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women ( 53% ).
In conclusion, this proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. ( Xagena )
Dawson S-J et al, N Engl J Med 2013; 368:1199-1209