BRST5:Phyllodes tumour

Breast Tumours (WHO Classification, 5th ed.)

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

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

Structure	Disease
Book	Breast Tumours (5th ed.)
Category	Fibroepithelial tumours and hamartomas of the breast
Family	Fibroepithelial tumours and hamartomas of the breast: Introduction
Type	Phyllodes tumour
Subtype(s)	N/A

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
7	Amp	7p11.2	EGFR			Amplification and/or rearrangement (most commonly loss of exons 2-7) in 33% of borderline and malignant tumors
7	Gain	7q				Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not observed in benign tumors
8	Gain	8q				Significantly more common in malignant vs. borderline tumors
9	Loss	9p21	CDKN2A, CDKN2B	P		Borderline and malignant tumors; associated with recurrence
10	Loss	10q23.31	PTEN	P		Mostly borderline and malignant tumors
13	Loss	13q14.2	RB1			Mostly borderline and malignant tumors

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)

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
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. MED12 is also frequently mutated in fibroadenoma, a related fibroepthelial tumor.
RARA		Oncogene	Common	P		Frequently co-mutated with MED12 and correlated with recurrence
TERT	promoter mutation	Oncogene	Common			No significant difference between benign, borderline, and malignant tumors. Frequently co-mutated with MED12.
CDKN2A	Inactivating mutations	Tumor suppressor gene	Recurrent			More common in malignant tumors.
EGFR	Exon 18-21 activating mutations	Oncogene	Recurrent	T		More common in malignant tumors
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.
NF1		Tumor suppressor gene	Recurrent			More common in malignant tumors.
PIK3CA		Oncogene	Recurrent			More common in borderline and malignant tumors.
RB1		Tumor suppressor gene	Recurrent			More common in malignant tumors. Gene deletions also common.
SETD2		Other	Recurrent			Frequently co-mutated with MED12. No significant difference between benign, borderline, and malignant tumors.
TP53	Inactivating mutations	Tumor suppressor gene	Recurrent			More common in malignant tumors. Germline mutations have been associated with phyllodes tumors.

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.

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

*Citation of this Page: “Phyllodes tumour”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/27/2025, https://ccga.io/index.php/BRST5:Phyllodes tumour.