Test Catalog

Test ID: ESR1    
Estrogen Receptor 1 (ESR1) Mutation Analysis, Tumor

Useful For Suggests clinical disorders or settings where the test may be helpful

Assisting in the clinical management of patients with metastatic breast cancer by identifying tumors with evolving resistance to endocrine therapy


Stratifying prognosis of metastatic breast cancer


This test is not useful for hematological malignancies.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The estrogen receptor 1 (ESR1) gene encodes an estrogen receptor that regulates cell growth through activation of downstream signaling pathways upon binding of estrogen. Tumors demonstrating estrogen receptor expression (ER-positive) are candidates for endocrine therapy such as selective estrogen receptor modulators (SERM) and aromatase inhibitors. ESR1 mutations are rarely observed in primary tumors; however, mutations in the ligand-binding domain of ESR1 have been reported at a higher frequency in ER-positive metastatic breast tumors. Preclinical data suggests that ESR1 mutations mitigate resistance to aromatase inhibitors and decrease sensitivity to SERMs and estrogen-receptor downregulators. Studies also suggest that ESR1 mutations are an independent indicator of poor prognosis.


This test assesses for somatic mutations in the ligand-binding domain of the ESR1 gene associated with acquired resistance to endocrine therapy (ie, aromatase inhibitors) in patients with ER-positive metastatic breast cancer.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretative report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test cannot differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk.


DNA variants of uncertain significance may be identified.


A negative (wild-type) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay.


Point mutations and small insertion/deletion mutations will be detected with in the ESR1 gene only. This test does not detect large single or multiexon deletions, or duplications or genomic copy number variants.


Rare polymorphisms may be present that could lead to false-negative or false-positive results. Test results should be interpreted in the context of clinical findings, tumor sampling and other laboratory data.

If results obtained do not match other clinical or laboratory findings, contact the laboratory for updated interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.


Reliable results are dependent on adequate specimen collection and processing. This test has been validated on cytology slides and formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.

Supportive Data

This next-generation sequencing assay detects somatic mutations that can be used to assist in the clinical management of metastatic breast cancer patients.


This assay has been shown to be very reproducible, having a 100% concordance for intra- and interassay reproducibility experiments. All somatic mutations that had been previously identified by various other molecular methods were detected by this assay during accuracy studies. No pathogenic variants were detected in known mutation negative samples.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Arenedos M, Vicier C, Loi S, et al: Precision medicine for metastatic breast cancer-limitations and solutions. Nat Rev Clin Oncol. 2015 Dec;12(12):693-704

2. Angus L, Beije N, Jager A, et al: ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients. Cancer Treat Rev. 2017 Jan;52:33-40

3. Gradishar WJ, Anderson BO, Balassanian R, et al: NCCN Guidelines Insights: Breast Cancer, Version 1.2017. J Natl Compr Canc Netw. 2017 Apr;15(4):433-451

4. Toy W, Shen Y, Won H, et al: ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013 Dec;45(12):1439-1445

5. Robinson DR, Wu YM, Vats P, et al: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013 Dec;45(12):1446-1451

6. Toy W, Weir H, Razavi P, et al: Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists. Cancer Discov. 2017 Mar;7(3):277-287