BRST5:Phyllodes tumour
Primary Author(s)*
Emilie Lalonde, PhD, London Health Sciences Center and Western University, London, Ontario, Canada
H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA
Katherine Geiersbach, MD, Mayo Clinic - Rochester, MN, USA
WHO Classification of Disease
(Instructions: This table’s content from the WHO book will be autocompleted.)
| Structure | Disease |
|---|---|
| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
WHO Essential and Desirable Genetic Diagnostic Criteria
(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)
| WHO Essential Criteria (Genetics)* | |
| WHO Desirable Criteria (Genetics)* | |
| Other Classification |
*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.
Related Terminology
(Instructions: The table will have the related terminology from the WHO autocompleted.)
| Acceptable | |
| Not Recommended |
Gene Rearrangements
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| EGFR | N/A | Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. | N/A | Recurrent | D, P, T | ||
Individual Region Genomic Gain/Loss/LOH
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| 1 | Gain | 1q (whole arm) | Frequency in benign tumors varies, up to 33% across studies[1][2][3] | |||
| 7 | Amp | 7p11.2 | EGFR | Amplification and/or rearrangement (most commonly loss of exons 2-7) in 33% of borderline and malignant tumors[4] | ||
| 7 | Gain | 7q | Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not observed in benign tumors[2] | |||
| 8 | Gain | 8q | Significantly more common in malignant vs. borderline tumors[1][2] | |||
| 9 | Loss | 9p21 | CDKN2A, CDKN2B | P | Borderline and malignant tumors; associated with recurrence[5] | |
| 10 | Loss | 10q23.31 | PTEN | P | Mostly borderline and malignant tumors[6][7][1][2] | |
| 13 | Loss | 13q14.2 | RB1 | Mostly borderline and malignant tumors[1][2][3] | ||
Characteristic Chromosomal or Other Global Mutational Patterns
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
Gene Mutations (SNV/INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| FLNA | Oncogene | Common | No significant difference between benign, borderline, and malignant tumors[5][8] | |||
| MED12 | G44 residue is a hotspot | Oncogene | Common | D | No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with RARA, TERT promoter, SETD2, EGFR.[9][8][5] MED12 is also frequently mutated in fibroadenoma, a related fibroepthelial tumor.[8] | |
| RARA | Oncogene | Common | P | Frequently co-mutated with MED12[5][10] and correlated with recurrence[5] | ||
| TERT | promoter mutation | Oncogene | Common | No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with MED12.[5][10] | ||
| CDKN2A | Inactivating mutations | Tumor suppressor gene | Recurrent | More common in malignant tumors.[5] | ||
| EGFR
|
Exon 18-21 activating mutations | Oncogene | Recurrent | T | More common in malignant tumors[5][4] | |
| KMT2D | Inactivating mutations | Tumor Suppressor Gene | Recurrent | Inactivation results in aberrant transcription regulation via epigenetic changes. No significant difference between benign, borderline, and malignant tumors.[5] | ||
| NF1 | Tumor suppressor gene | Recurrent | More common in malignant tumors.[5][10] | |||
| PIK3CA | Oncogene | Recurrent | More common in borderline and malignant tumors.[5][10] | |||
| RB1 | Tumor suppressor gene | Recurrent | More common in malignant tumors. Gene deletions also common.[10][5] | |||
| SETD2 | Other | Recurrent | Frequently co-mutated with MED12. No significant difference between benign, borderline, and malignant tumors.[10][5] | |||
| TP53 | Inactivating mutations | Tumor suppressor gene | Recurrent | More common in malignant tumors.[5] Germline mutations have been associated with phyllodes tumors.[11] |
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
Put your text here
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
Next generation sequencing. Chromosomal microarray for CNV detection can be considered if NGS testing does not call CNVs. Detection of CNVs can help differentiate between fibroadenomas and phyllodes tumors. FISH for EGFR amplification can also be considered in the absence of chromosome microarray or appropriate NGS assays.
Familial Forms
Patients with Li-Fraumeni syndrome (germline TP53 pathogenic mutations) are at increased risk of phyllodes tumor.
Additional Information
Due to the rarity of phyllodes tumors, most genomic studies are limited in number, and studies including patient follow-up information are very rare. Thus, the true mutation rate for rare events may vary compared to the numbers presented. In addition, very few studies have evaluated the prognostic value of genomic abnormalities.
Links
https://www.pathologyoutlines.com/topic/breastphyllodesgeneral.html
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s):
References
- ↑ 1.0 1.1 1.2 1.3 Laé, Marick; et al. (2016-12). "Whole-genome profiling helps to classify phyllodes tumours of the breast". Journal of Clinical Pathology. 69 (12): 1081–1087. doi:10.1136/jclinpath-2016-203684. ISSN 1472-4146. PMID 27207013. Check date values in:
|date=(help) - ↑ 2.0 2.1 2.2 2.3 2.4 Jones, A. M.; et al. (2008-04). "A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence". The Journal of Pathology. 214 (5): 533–544. doi:10.1002/path.2320. ISSN 0022-3417. PMID 18288784. Check date values in:
|date=(help) - ↑ 3.0 3.1 Lv, Shuhua; et al. (2008-12). "Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study". Breast Cancer Research and Treatment. 112 (3): 411–418. doi:10.1007/s10549-007-9876-1. ISSN 1573-7217. PMID 18189161. Check date values in:
|date=(help) - ↑ 4.0 4.1 Gatalica, Zoran; et al. (2016-01-12). "Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast". Oncotarget. 7 (2): 1707–1716. doi:10.18632/oncotarget.6421. ISSN 1949-2553. PMC 4811491. PMID 26625196.
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 Tsang, Julia Y.; et al. (2022-10). "Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis". Pathology. 54 (6): 678–685. doi:10.1016/j.pathol.2022.03.008. ISSN 1465-3931. PMID 35691725 Check
|pmid=value (help). Check date values in:|date=(help) - ↑ Kim, Ji-Yeon; et al. (2018-02). "Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast". Translational Oncology. 11 (1): 18–23. doi:10.1016/j.tranon.2017.10.002. ISSN 1936-5233. PMC 5684533. PMID 29145046. Check date values in:
|date=(help) - ↑ Nozad, Sahar; et al. (2017-04). "Comprehensive genomic profiling of malignant phyllodes tumors of the breast". Breast Cancer Research and Treatment. 162 (3): 597–602. doi:10.1007/s10549-017-4156-1. ISSN 1573-7217. PMID 28210881. Check date values in:
|date=(help) - ↑ 8.0 8.1 8.2 Tan, Jing; et al. (2015-11). "Genomic landscapes of breast fibroepithelial tumors". Nature Genetics. 47 (11): 1341–1345. doi:10.1038/ng.3409. ISSN 1546-1718. PMID 26437033. Check date values in:
|date=(help) - ↑ Cani, Andi K.; et al. (2015-04). "Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors". Molecular cancer research: MCR. 13 (4): 613–619. doi:10.1158/1541-7786.MCR-14-0578. ISSN 1557-3125. PMC 4936398. PMID 25593300. Check date values in:
|date=(help) - ↑ 10.0 10.1 10.2 10.3 10.4 10.5 Yeong, Joe; et al. (2017-12). "A genetic mutation panel for differentiating malignant phyllodes tumour from metaplastic breast carcinoma". Pathology. 49 (7): 786–789. doi:10.1016/j.pathol.2017.07.011. ISSN 1465-3931. PMID 29066183. Check date values in:
|date=(help) - ↑ Rosenberger, Laura H.; et al. (2020-10). "Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing". Annals of Surgical Oncology. 27 (10): 3633–3640. doi:10.1245/s10434-020-08480-z. ISSN 1534-4681. PMC 9945652 Check
|pmc=value (help). PMID 32504368 Check|pmid=value (help). Check date values in:|date=(help)