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.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
When this test is ordered, slide review will always be performed at an additional charge.
Polymerase Chain Reaction (PCR)-Based Next-Generation Sequencing
ESR1
ER
ER positive
Estrogen receptor 1
Endocrine therapy
Metastatic breast cancer
Next Gen Sequencing
NGS
When this test is ordered, slide review will always be performed at an additional charge.
Varies
Pathology report (final or preliminary) at minimum containing the following information must accompany specimen in order for testing to be performed:
1. Patient name
2. Block number-must be on all blocks, slides and paperwork (can be handwritten on the paperwork)
3. Tissue collection date
4. Source of the tissue
This assay requires at least 20% tumor nuclei.
-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue144 mm(2)
-Minimum amount of tumor area: tissue 36 mm(2).
-These amounts are cumulative over up to 10 unstained slides and must have adequate percent tumor nuclei.
-Tissue fixation: 10% neutral buffered formalin, not decalcified
-For specimen preparation guidance, see Tissue Requirement for Solid Tumor Next-Generation Sequencing in Special Instructions. In this document, the sizes are given as 4mm x 4mm x 10 slides as preferred: approximate/equivalent to 144 mm(2) and the minimum as 3mm x 1mm x 10 slides: approximate/equivalent to 36mm(2).
Preferred:
Specimen Type: Tissue block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block with acceptable amount of tumor tissue.
Acceptable:
Specimen Type: Tissue slide
Slides: 1 stained and 10 unstained
Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides with 5-micron thick sections of the tumor tissue.
Note: The total amount of required tumor nuclei can be obtained by scraping up to 10 slides from the same block.
Specimen Type: Cytology slide (direct smears or ThinPrep)
Slides: 1 to 3 slides
Collection Instructions: Submit 1 to 3 slides stained and cover slipped with a preferred total minimum of 5000 total nucleated cells, minimum of 3000 nucleated cells.
Note: Glass coverslips are preferred; plastic coverslips are acceptable but will result in longer turnaround times.
Additional Information: Cytology slides will not be returned.
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.
See Specimen Required
Other | Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Frozen | |||
Refrigerated |
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.
When this test is ordered, slide review will always be performed at an additional charge.
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.
An interpretative report will be provided.
An interpretive report will be provided.
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.
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.
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
Next-generation sequencing is performed to test for the presence of a mutation in targeted regions of the ESR1 gene.(Unpublished Mayo method)
Gene | GenBank Accession Number | Nucleotide Start | Nucleotide End | Chromosome | Exon | Codons |
ESR1 | NM_000125 | 152415449 | 152415563 | Chromosome 6 | Exon 7 | 457-471 |
152419879 | 152419997 | Exon 8 | 522-562 |
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
81479
88381
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
ESR1 | ESR1 Mutation Analysis, Tumor | In Process |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
92381 | Result Summary | 50397-9 |
92382 | Result | 82939-0 |
92383 | Interpretation | 69047-9 |
92384 | Additional Information | 48767-8 |
92385 | Specimen | 31208-2 |
92386 | Source | 31208-2 |
92387 | Tissue ID | 80398-1 |
92388 | Released By | 18771-6 |