Analysis of circulating tumor DNA to monitor metastatic breast cancer
Sarah-Jane Dawson, Dana W Y Tsui, Muhammed Murtaza, Heather Biggs, Oscar M Rueda, Suet-Feung Chin, Mark J Dunning, Davina Gale, Tim Forshew, Betania Mahler-Araujo, Sabrina Rajan, Sean Humphray, Jennifer Becq, David Halsall, Matthew Wallis, David Bentley, Carlos Caldas, Nitzan Rosenfeld, Sarah-Jane Dawson, Dana W Y Tsui, Muhammed Murtaza, Heather Biggs, Oscar M Rueda, Suet-Feung Chin, Mark J Dunning, Davina Gale, Tim Forshew, Betania Mahler-Araujo, Sabrina Rajan, Sean Humphray, Jennifer Becq, David Halsall, Matthew Wallis, David Bentley, Carlos Caldas, Nitzan Rosenfeld
Abstract
Background: 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.
Methods: We 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. We 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.
Results: 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%).
Conclusions: This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. (Funded by Cancer Research UK and others.).
Source: PubMed