ESR1 Methylation Measured in Cell-Free DNA to Evaluate Endocrine Resistance in Metastatic Breast Cancer Patients

Manouk K. Bos*, Teoman Deger, Stefan Sleijfer, John W.M. Martens, Saskia M. Wilting*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

ESR1 methylation was proposed as mechanism for endocrine resistance in metastatic breast cancer patients. To evaluate its potential as a minimally invasive biomarker, we investigated the feasibility of measuring ESR1 methylation in cell-free DNA (cfDNA) and its association with endocrine resistance. First, we provided evidence that demethylation in vitro restores ER expression. Subsequently, we found that ESR1 methylation in cfDNA was not enriched in endocrine-resistant versus endocrine-sensitive patients. Interestingly, we found a correlation between ESR1 methylation and age. Publicly available data confirm an age-related increase in ESR1 methylation in leukocytes, confounding the determination of the ESR1 methylation status of tumors using cfDNA.

Original languageEnglish
Article number5631
JournalInternational Journal of Molecular Sciences
Volume23
Issue number10
DOIs
Publication statusPublished - 18 May 2022

Bibliographical note

Funding: This research was funded by the Dutch Cancer Society (project no. NKB-EMCR-2016-108154).

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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