ESR1 Mutations in Breast Cancer

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Breast cancer
ESR1m

ESR1m

Jump to:

Role of ESR1
Prevalence
Testing Recommendations
ctDNA-Mediated Testing to Detect ESR1m
Considerations for Your Practice
Helpful Resources

Role of ESR1

ESR1 is the gene encoding estrogen receptor alpha (ERα), a key driver of hormone-dependent cancers¹

This is particularly evident in estrogen receptor-positive (ER+) breast cancer, including HR+/HER2-, where ESR1 promotes tumor growth.

ESR1, estrogen receptor 1; HR+, Hormone Receptor-Positive; HER2-, human epidermal growth factor receptor-negative.

ESR1 mutations may promote breast cancer tumor growth through estrogen-mediated transcriptional regulation³

Acquired resistance

ESR1m is an acquired mutation that evolves frequently through resistance to endocrine therapy (ET).^4-7

Proactive identification and ESR1m interpretation

Identify ESR1m as quickly as possible, as these mutations may lead to disease progression and poorer patient outcomes.⁴

ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation.

ESR1 Mutation Prevalence: ESR1 Mutations Are Not Commonly Present at Diagnosis of Metastatic Breast Cancer (mBC) in Patients Who Are Endocrine Therapy (ET) Naive^3-8

~6%

of patients who are ET naive carry an ESR1 mutation, which is detected when tested at mBC diagnosis^3,8

Exposure to aromatase inhibitors (AIs) during 1L treatment leads to the emergence of endocrine resistance^8,9

Among patients who typically receive AIs in the metastatic setting

nearly

40%

acquire ESR1 mutations^4,9

1L, first-line; AI, aromatase inhibitor.

Testing Recommendations for ESR1m^7,9-13

ESR1 mutations may signal development of endocrine resistance⁹

Early and routine testing for ESR1m in addition to ESR1m analysis provides a pivotal opportunity to impact patient outcomes in breast cancer because its emergence precedes radiographic or clinical evidence of disease progression.⁷

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) recommend evaluating ESR1m status through NGS or PCR¹⁰

NCCN Guidelines recommend testing ESR1m through liquid biopsy (blood samples).¹⁰

ctDNA is a validated method for identifying ESR1m.^11-13

NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; PCR, polymerase chain reaction.

ESR1m Testing Options Overview^14-32

Laboratory	Assay name/platform	Technology	Sensitivity (VAF)	Sample type	Turnaround time	FDA-approved test
Guardant Health	Guardant360^® Transpose CDx	NGS (Large panel CGP)	0.3-1.0%	Plasma (ctDNA)	7 days
Foundation Medicine	FoundationOne^® Liquid CDx	NGS (Large panel CGP)	0.33-0.5%	Plasma (ctDNA)	<10 days
Thermo Fisher Scientific	Oncomine Precision Assay	NGS (Small panel)	0.25%	Plasma (ctDNA)	1 day
Caris Life Sciences	Caris Assure^® Liquid Biopsy^®	NGS (Large panel CGP)	0.05-0.45%	Plasma (ctDNA)	7–10 days	RUO
Labcorp	Labcorp Plasma Complete Portfolio	NGS (Large panel CGP)	0.1-0.5%	Plasma (ctDNA)	8 days	RUO
NeoGenomics	NEO PanTracer LBx Assay	NGS (Large panel CGP)	0.17-0.31%	Plasma (ctDNA)	7 days	RUO
Roche	AVENIO ctDNA Expanded Kit V2	NGS (Large panel CGP)	0.5%	Plasma (ctDNA)	5 days	RUO
Thermo Fisher Scientific	Oncomine Pan-Cancer Cell-Free Assay	NGS (Large panel CGP)	0.1%	Plasma (ctDNA)	2 days	RUO
Tempus	Tempus^® xF/xF+ Liquid Biopsy	NGS (Large panel CGP)	0.25%	Plasma (ctDNA)	7 days	RUO
Pillar Biosciences	OncoReveal^TM Essential LBx	NGS (Small panel)	0.1%	Plasma (ctDNA)	~3 days	RUO
Thermo Fisher Scientific	Oncomine^TM Breast cfDNA Assay	qPCR/dPCR	0.1%	Plasma (ctDNA)	2 days	RUO
BioRad Laboratories	ddPLEX ESR1 Mutation Detection Kit	dPCR	0.010-0.025%	Plasma (ctDNA)	<8 hours	RUO
APIS Assay Technologies	ESR1 Mutations qPCR Kit	qPCR	0.500%	Plasma (ctDNA)	2 hours	RUO
Asuragen (Bio-Techne)	Quantidex^® qPCR ESR1 exoMutation Panel	qPCR	0.120-0.150%	Plasma (ctDNA)	5–6 hours	RUO
QIAGEN	QIAcuity^® Digital PCR	dPCR	NR	Plasma (ctDNA)	~8 hours	RUO
Stilla Technologies	Stilla ESR1 (17 mutations) Crystal Digital PCR^® Assay	dPCR	0.120–0.150%	Plasma (ctDNA)	Not specified	RUO
APIS Assay Technologies	APIS ESR1 dPCR Kit	dPCR	0.100%	Plasma (ctDNA)	4 hours	RUO

CDx, companion diagnostic; CGP, comprehensive genomic profiling; ctDNA, circulating tumor DNA; ddPCR, droplet digital polymerase chain reaction; dPCR, digital polymerase chain reaction; FDA, US Food and Drug Administration; LBx, liquid biopsy; NGS, next generation sequencing; qPCR, quantitative polymerase chain reaction; RUO, research use only; VAF, variant allelle frequency.

Utilizing ctDNA-Mediated Testing to Detect ESR1m¹¹

ctDNA-mediated testing with liquid biopsy (blood samples) identifies tumor-specific genomic alterations in patients with metastatic breast cancer
NGS panel tests should be performed on blood samples

NCCN Guidelines do not recommend testing with primary archived tissue given the acquired nature of ESR1m.¹⁰

Benefits of ctDNA assays to detect mutations¹¹

Less invasive
Analytically validated
Assesses multiple tumor locations in breast cancer

ctDNA testing options overview^24,30,32-34

Method	Turnaround time	Results	Potential impact
NGS	7–14 days	Comprehensive genomic data	More informed decision-making
PCR	1 day	Efficient ESR1 results only(single-gene test)	Faster decision-making

Detailed PCR testing overview³⁵

PCR method	Detection timing	Quantification type	Assay type
qPCR	Real-time	Relative	Quantitative with standard curves
dPCR	End-point	Absolute	Qualitative
ddPCR	End-point	Absolute	Qualitative

When determining which method is appropriate for your patient and practice, consider the functional differences between timing, cost, and reporting characteristics.

Considerations for Your Practice

Collaboration between pathologists, medical oncologists, or tumor boards on ESR1m testing may help improve patient care.^7,36

Integrating ctDNA-mediated ESR1m testing into pathology workflows may help to identify the emergence of endocrine resistance, a valuable insight for your care team
Evaluating your lab’s capacity for ctDNA-mediated ESR1m testing, especially as demand increases with guideline-based adoption of liquid biopsy testing, enables preparedness
Choosing a digital form of ordering vs manual forms improves your ordering experience

View educational resources that can help facilitate testing conversations between you and your patients with breast cancer in the Resource Library.

Helpful Resources

Check out these featured resources on ESR1m biomarker testing in metastatic breast cancer.

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Xia S, Lin Q. Estrogen receptor bio-activities determine clinical endocrine treatment options in estrogen receptor-positive breast cancer. Technol Cancer Res Treat. 2022;21:15330338221090351.
Clatot F, Perdrix A, Beaussire L, et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. Breast Cancer Res. 2020;22(1):56. doi:10.1186/s13058-020-01290-x
Grinshpun A, Chen V, Sandusky ZM, Fanning SW, Jeselsohn R. ESR1 activating mutations: from structure to clinical application. Biochim Biophys Acta Rev Cancer. 2023;1878(1):188830. doi:10.1016/j.bbcan.2022.188830
Allouchery V, Beaussire L, Perdrix A, et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res. 2018;20(1):40. doi:10.1186/s13058-018-0968-0
Beije N, Sieuwerts AM, Kraan J, et al. Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients. Mol Oncol. 2018;12(1):48-57. doi:10.1002/1878-0261.12147
Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol. 2016;2(10):1310-1315. doi:10.1001/jamaoncol.2016.1279
Fribbens C, Garcia Murillas I, Beaney M, et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann Oncol. 2018;29(1):145-153. doi:10.1093/annonc/mdx483
Bhave MA, Quintanilha JCF, Tukachinsky H, et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(−) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real‑world practice. Breast Cancer Res Treat. 2024;207(3):599-609. doi:10.1007/s10549-024-07376-w
Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. doi:10.1186/s13058-021-01462-3
Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines^® insights: breast cancer, version 4.2023. J Natl Compr Canc Netw. 2023;21(6):594-608. doi:10.6004/jnccn.2023.0031
Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022;33(8):750-768. doi:10.1016/j.annonc.2022.05.520.
Shaw J, Page K, Ambasger B, et al. Serial postoperative ctDNA monitoring of breast cancer recurrence. Abstract 562. J Clin Oncol. 2022;40(16):562. doi:10.1200/JCO.2022.40.16_suppl.562
Gawel SH, Jackson L, Jeanblanc N, Davis GJ. Current and future opportunities for liquid biopsy of circulating biomarkers to aid in early cancer detection. J Cancer Metastasis Treat. 2022;8(5):26. doi:10.20517/2394-4722.2022.13
Guardant Health. Technical information. Accessed October 17, 2025. https://www.guardantcomplete.com/assets/pdf/Guardant360-CDx-Technical-Information-US.pdf
Foundation Medicine. FoundationOne^®Liquid CDx: Technical specifications. Accessed October 17, 2025. https://www.foundationmedicine.com/sites/default/files/media/documents/2023-10/F1LCDx_Technical_Specs_072021-2.pdf
Foundation Medicine. Our Proven Portfolio. That’s Our Foundation. Accessed November 19, 2025. https://www.foundationmedicine.com/portfolio
ThermoFisher. Oncomine Precision Assay on the Genexus System. Accessed October 17, 2025. https://www.thermofisher.com/us/en/home/clinical/preclinical-companion-diagnostic-development/oncomine-oncology/oncomine-precision-assay.html
Caris Life Sciences. Caris Assure: Technical Specifications 2025. https://d35ibn74wp9llh.cloudfront.net/000d31fd-e04b-4936-be1c-11acbe19e1ec/f55d2c47-6ce2-4429-ac40-14e89e5e7b10/f55d2c47-6ce2-4429-ac40-14e89e5e7b10_source__v.pdf
Labcorp. Labcorp Plasma Complete Portfolio Brochure. Accessed October 30, 2025. https://oncology.labcorp.com/sites/default/files/2025-01/683903_DX_BRO_PlasmaComplete_FINAL-0125%20%281%29.pdf
NeoGenomics. PanTracer for Pharma Partners. Accessed October 31, 2025. https://www.neogenomics.com/PanTracer-LDT/
Pipinikas C, Patel KB, Vyas H, et al. Analytical validation and clinical performance of a plasma-based CGP assay, NEO | PanTracer LBx. J Clin Oncol. 2025;43(16):e15047. doi:10.1200/JCO.2025.43.16_suppl.e15047
Roche. AVENIO ctDNA Expanded Kit V2. Accessed October 30, 2025. https://sequencing.roche.com/us/en/products/group/avenio-ctdna-expanded-kits.html#productInfo
ThermoFisher. Oncomine Pan-Cancer Cell-Free Assay. Accessed October 30, 2025. https://www.thermofisher.com/order/catalog/product/A31183
Tempus. Tempus xF/xF+ liquid biopsy. Accessed October 17, 2025. https://www.tempus.com/oncology/genomic-profiling/xf/
Pillar Biosciences. Essential LBx Panel. Accessed October 30, 2025. https://www.pillarbiosci.com/wp-content/uploads/2024/09/MK-0050-oncoReveal-Essential-LBx-5.2024_v1.3.pdf
Thermo Fisher Scientific. Oncomine™ Breast cfDNA research assay v2. Accessed November 19, 2025. https://www.thermofisher.com/order/catalog/product/A35865
BioRad Laboratories. ddPLEX ESR1 Mutation Detection Kit. Accessed October 31, 2025. https://www.bio-rad.com/en-us/product/ddplex-esr1-mutation-detection-kit?ID=898d06be-e112-8974-31f4-0c1986580c7b
APIS Assay Technologies. ESR1 Mutations qPCR Kit. Accessed October 31, 2025. https://static1.squarespace.com/static/5e8c8b846bab995ffb19007a/t/6839cfc32132492fa710cc80/1748619204140/APIS+ESR1+qPCR+Kit+Flyer.pdf
Asuragen (Bio-Techne). QuantideX^® qPCR ESR1 exoMutation Kit. Accessed October 30, 2025. https://asuragen.com/wp-content/uploads/2025/07/quantidex-qpcr-esr1-exomutation-kit-0625.pdf
QIAGEN. QiAcuity Digital PCR. Accessed October 30, 2025. https://www.qiagen.com/us/products/instruments-and-automation/pcr-instruments/qiacuity-digital-pcr-system?cmpid=CM_PCR_dPCR_Traffic_0123_SEA_GA_NA&s_kwcid=AL!16953!3!701019953208!p!!g!!qiagen%20qiacuity&gad_source=1&gad_campaignid=16142545878&gbraid=0AAAAAD-RrCzuBzTuKHor8xjHwawiP0lpK&gclid=EAIaIQobChMIirCX6Y7WkAMVu2dHAR1I5A8bEAAYASAAEgLlN_D_BwE
Stilla Technologies. ESR1 (17 Mutations) Crystal Digital PCR^® Assay. Accessed October 30, 2025. https://go.stillatechnologies.com/assay/esr1-17-mutations-crystal-digital-pcr-r-assay
APIS Assay Technologies. APIS ESR1 dPCR Kit. Accessed October 30, 2025. https://www.apisassay.com/apis-esr1-dpcr-kit
CD Genomics. Hybridization capture vs PCR amplification – the two enrichment strategies in NGS. Accessed September 9, 2024. https://www.cd-genomics.com/microbioseq/hybridization-capture-vs-pcr-amplification.html#:~:text=Generally% 20speaking%2C%20amplicon%2Dbased%20approaches,above%20factors%20worth%20careful%20consideration
Lee N, Park MJ, Song W, Jeon K, Jeong S. Currently applied molecular assays for identifying ESR1 mutations in patients with advanced breast cancer. Int J Mol Sci. 2020;21(22):8807. doi:10.3390/ijms21228807
Quan PL, Sauzade M, Brouzes E. dPCR: a technology review. Sensors (Basel). 2018;18(4):1271. doi:10.3390/s18041271
Guerini-Rocco E, Venetis K, Cursano G, et al. Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer. Crit Rev Oncol Hematol. 2024;201:104427.

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Role of ESR1

Acquired resistance

Proactive identification and ESR1m interpretation

ESR1 Mutation Prevalence: ESR1 Mutations Are Not Commonly Present at Diagnosis of Metastatic Breast Cancer (mBC) in Patients Who Are Endocrine Therapy (ET) Naive3-8

Testing Recommendations for ESR1m7,9-13

Footnotes

Utilizing ctDNA-Mediated Testing to Detect ESR1m11

Considerations for Your Practice

Helpful Resources

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ESR1 Mutation Prevalence: ESR1 Mutations Are Not Commonly Present at Diagnosis of Metastatic Breast Cancer (mBC) in Patients Who Are Endocrine Therapy (ET) Naive^3-8

Testing Recommendations for ESR1m^7,9-13

Utilizing ctDNA-Mediated Testing to Detect ESR1m¹¹