A systematic review of the use of circulating cell-free DNA dynamics to monitor response to treatment in metastatic breast cancer patients

Elisabeth M. Jongbloed*, Teoman Deger, Stefan Sleijfer, John W.M. Martens, Agnes Jager, Saskia M. Wilting

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

7 Citations (Scopus)
13 Downloads (Pure)

Abstract

Monitoring treatment response in metastatic breast cancer currently consists mainly of radiological and clinical assessments. These methods have high inter-observer variation, suboptimal sensitivity to determine response to treatment and give little insight into the biological characteristics of the tumor. Assessing circulating tumor DNA (ctDNA) over time could be employed to address these limitations. Several ways to quantify and characterize ctDNA exist, based on somatic mutations, copy number variations, methylation, and global circulating cell-free DNA (cfDNA) fragment sizes and concentrations. These methods are being explored and technically validated, but to date none of these methods are applied clinically. We systematically reviewed the literature on the use of quantitative ctDNA measurements over time to monitor response to systemic therapy in patients with metastatic breast cancer. Cochrane, Embase, PubMed and Google Scholar databases were searched to find studies focusing on the use of cfDNA to longitudinally monitor treatment response in advanced breast cancer patients until October 2020. This resulted in a total of 33 studies which met the inclusion criteria. These studies were heterogeneous in (pre-)processing procedures, applied techniques and design. An association between ctDNA and treatment response was found in most of the included studies, independent of the applied assay. To implement ctDNA-based response monitoring into daily clinical practice for metastatic breast cancer patients, sample (pre-) processing procedures need to be standardized and large prospectively collected sample cohorts with well annotated clinical follow-up are required to establish its clinical validity.

Original languageEnglish
Article number1811
JournalCancers
Volume13
Issue number8
DOIs
Publication statusPublished - 2 Apr 2021

Bibliographical note

Funding Information:
This work was funded by the Dutch Cancer Society (KWF), grant number 12039, the Daniel den Hoed foundation and Cancer GenomiCs.nl (CGC.nl).The authors wish to thank Maarten F.M. Engel and Sabrina Gunput from the Erasmus MC Medical Library for developing and updating the search strategies.


Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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