Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing

Yanagawa, Tetsuo; Kagara, Naofumi; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

doi:10.1007/s10549-017-4190-z

Cited by 33 publications

(22 citation statements)

References 30 publications

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“…17,19 Previous studies showed that ESR1 mutations were less frequently observed in patients who received AI treatment only at an adjuvant setting, suggesting the clonal selection of ESR1-mutant cancer cells under the estrogen-deprived condition in the metastatic tumors, but not in the small number of tumors during adjuvant treatment. 17,19,23 A previous study reported that AI resistance might be associated with ESR1 mutation, and therefore ESR1mutant patients should avoid subsequent AI treatment. 17 Another study also found that the overall survival time of ESR1 mutation patients (i.e., D538G, 25.99 months; Y537S, 19.98 months; both D538G and Y537S mutations, 15.15 months) was shorter than ESR1 wild-type patients (32.1 months).…”

Section: Discussionmentioning

confidence: 99%

“…20 NGS has been used to detect novel ESR1 mutations in ctDNA with a reported error rate as low as 0.01%. [21][22][23] Therefore, the purpose of this study was to perform NGS assay on all exons of the ESR1 gene taken from primary tumor samples and blood samples of metastatic breast cancer to identify the prevalence of ESR1 mutation in Chinese breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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<p>Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer</p>

Zhu

Ren

Wang

et al. 2020

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Background: ESR1 mutation and its possible relation to endocrine therapy resistance in ERpositive breast cancers have been studied with respect to genetic sequencing data from Western patients but rarely from Chinese patients. This study aimed to investigate the prevalence of ESR1 mutation in Chinese primary and metastatic ER-positive breast cancer. Methods: Tumor samples from 297 primary breast cancer (PBC) patients and blood samples from 43 metastatic breast cancer (MBC) patients were obtained to perform whole exon sequencing of the ESR1 gene through next-generation sequencing (NGS). Clinicopathological features of MBC patients were listed and grouped to explore potential factors in ESR1 mutations. Results: A total of 15 ESR1 variations, including 11 point mutations, 1 in-frame deletion mutation, 1 synonymous mutation, and 2 amplifications were identified in 13 patients. The ESR1 mutation rate was 1% (3/297) in PBC patients and 18.6% (8/43) in MBC patients. All ESR1 point mutations occurred in the estrogen receptor ligand-binding domain. Six (54.5%) of the 11 point mutations were hotspot mutations. Among all MBC patients, the ESR1 mutation rate in those who had a treatment history using aromatase inhibitors (AI) was significantly higher than those who did not (25.8% versus 0%, P=0.015). Moreover, the ESR1 mutation rate in those who received AI treatment over a period of 12 months was significantly higher than in those whose treatment lasted less than 12 months [36.3% versus 0%, P<0.001]. Conclusion: ESR1 mutations were more frequently observed in the circulating cell-free DNA of MBC patients than in PBC patients among the Chinese cohort, and higher among those pretreated with AI, suggesting that such mutations may undergo selection during AI treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer</p>

Zhu

Ren

Wang

et al. 2020

OTT

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“…For instance, the concept of "mutational status" relies on the definition of thresholds that define how frequent an alteration (such as a specific LBD-ER mutation) must be to be classified as positive. Although detection technologies already allow for ultrasensitive measurements (see next section), there is a current lack of consensus in the definition of cut-offs for mutation positivity [132,141,142,239,240] and studies are needed to establish rigorous and standardised thresholds. Larger studies with paired blood and metastatic tumour biopsy samples are also required to investigate the correlation in biomarker levels between both sample types and ensure that detection in LBs does not misrepresent the actual frequency of genetic alterations in the metastases.…”

Section: Liquid Biopsies For Better Samplingmentioning

confidence: 99%

“…Improved tools include the development of sequencing methods with reduced background error and greater sensitivity for screening of liquid biopsies [241,[244][245][246][247]. PCR-based methods for allele-specific mutant detection have also been developed [245,246,248,249] and digital droplet PCR (ddPCR) in particular has been used for ESR1 mutation assessment in many of the studies to date [142,145,253,[235][236][237]239,240,[250][251][252]]. somatic mutations (see Figure 2 for summary diagram).…”

Section: Improved Detection Technologiesmentioning

confidence: 99%

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Martínez-Pérez

Turnbull

Dixon

2018

Expert Review of Anticancer Therapy

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Introduction:In breast cancer, oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment and the constant evolution of the disease invariably leads to resistance to treatment. Areas covered:We summarise genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis. Expert commentary:While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardise assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.

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“…Mutations in the ESR1 gene, encoding ERα, found in about 20% of recurrent and metastatic BCa patients treated with endocrine therapies [18], whereas ESR1 mutations are extremely rare in primary BCa [18]. Moreover, ESR1 mutations are currently considered as novel mechanisms of resistance to endocrine therapies [19]. AKT1 is related with altered cell migration and invasion in several mammalian systems.…”

Section: Other Important Genes In Breast Cancermentioning

confidence: 99%

Focus on Candidate Genes in Molecular Genetics Analyses for Breast Cancer Treatment

Dirican¹

2017

Tumor Res

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Although a remarkable rise in the depth of our understanding and management of breast cancer (BCa) in the last decade, this matter is still a major public health problem the entire world. But, researchers investigate about reason of BCa. Especially, they detected some important genes (BRCA1/2, PIK3CA, MED12, CDH1, TP53, PTEN or SALL4) for BCa diagnosis or treatment. For this reason we reviewed about roles, functions or effects of these crucial genes in BCa. To determine candidate genes important in BCa processes need to be further analysis with a greater number of patients.

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Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing

Abstract: Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

Cited by 33 publications

References 30 publications

<p>Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer</p>

<p>Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer</p>

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Focus on Candidate Genes in Molecular Genetics Analyses for Breast Cancer Treatment

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