Dawson et al in a NEJM article report on their research on
monitoring tumor burden on patients with metastatic breast cancer by means of
detecting circulating cell-free DNA carrying tumor specific alterations.
A total of 52 women with metastatic
breast cancer were recruited, 30 of whom had genomic alterations suitable for
monitoring. Serial blood samples were collected at intervals of 3 or more
weeks. Computed tomography (CT) was performed to document response to treatment.
They compared the radiographic imaging of tumors with the assay of circulating
tumor DNA, CA 15-3, and circulating tumor cells in the 30 women who were
receiving systemic therapy. They used targeted or whole-genome sequencing to
identify somatic genomic alterations and designed personalized assays to
quantify circulating tumor DNA in 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%).
Metastatic breast cancer remains an
incurable but treatable disease.
Effective monitoring of treatment response is essential in order to
avoid continuing ineffective therapies and to prevent side effects. Their research showed that circulating tumor DNA is an
informative, specific, and sensitive biomarker of metastatic breast cancer.
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