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. 2025 Oct;487(4):895-899.
doi: 10.1007/s00428-024-03942-1. Epub 2024 Oct 11.

Diagnostic utility of ESR1 mutation detection in liquid biopsy of metastatic breast cancer patients

Maria Sandbothe  1 , Britta Hasemeier  1 , Elisa Schipper  1 , Nora Schaumann  1 , Hans Kreipe  1 , Ulrich Lehmann  1 , Stephan Bartels  2
Affiliations

Diagnostic utility of ESR1 mutation detection in liquid biopsy of metastatic breast cancer patients

Maria Sandbothe et al. Virchows Arch. 2025 Oct.

Abstract

Molecular analysis of circulating cell-free DNA (cfDNA) extracted from peripheral blood plasma samples of metastatic breast cancer (BC) patients is of rising interest to find optimal therapeutic strategies. Detection of emerging resistance mutations against endocrine therapy is possible with this approach. Here we present the applicability of a laboratory-developed NGS assay in molecular pathology routine diagnostic, covering four genes with therapeutic (ESR1, PIK3CA, ERBB2) and prognostic (TP53) consequences in metastatic BC. We analyzed 162 liquid biopsy samples and 25 corresponding metastases from metastatic BC patients. In the liquid biopsies, we detected ESR1 mutations in 42 cases (25.9%) and ERBB2 mutations in six cases (3.7%), arguing for a change in therapy to fulvestrant, elacestrant, or neratinib. Furthermore, 17 cases had detectable TP53 mutations, associated with resistance against endocrine therapy. We conclude that liquid biopsy testing is a noninvasive, sensitive, and helpful method to optimize therapeutic decisions in metastatic BC.

Keywords: ESR1; Breast cancer; Elacestrant; Liquid biopsy; Metastasis.

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Conflict of interest statement

Declarations. Ethics approval: Retrospective analyses of anonymized diagnostic left over material have been approved by the local ethics committee (Hannover Medical School, Germany, Head: Prof. Schmidt). Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Distribution of detected mutations in 162 liquid biopsy samples within functional domains of the genes ERBB2, ESR1, PIK3CA, and TP53. If a specific mutation was found in more than one sample, the total number is given in parentheses
Fig. 2
Fig. 2
Clinical features and gene mutations detected in liquid biopsy samples of 162 BC patients (created in https://www.cbioportal.org/oncoprinter). For details, see supplementary Table 2
Fig. 3
Fig. 3
Four sub-clonal ESR1 hotspot mutations in trans (p.Y537N/S/C and p.D538G) from case no. 28. The p.E380Q mutation in exon 6 is not shown
See this image and copyright information in PMC

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