Papillary ductal carcinoma in situ

Breast Tumours (WHO Classification, 5th ed.)

Primary Author(s)*

Sresi Singh

WHO Classification of Disease

Structure	Disease
Book	Breast Tumours (5th ed.)
Category	Epithelial tumours of the breast
Family	Papillary neoplasms: Introduction
Type	Papillary ductal carcinoma in situ
Subtype(s)	N/A

Related Terminology

Acceptable	Papillary carcinoma in situ; intraductal papillary ductal carcinoma in situ
Not Recommended	Intracystic papillary ductal carcinoma; encapsulated/solid papillary carcinoma

Gene Rearrangements

No recurrent gene rearrangements have been identified in papillary DCIS, which is primarily characterized by mutations and copy number alterations.

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

Individual Region Genomic Gain/Loss/LOH

Copy-number alterations are common genomic events in ductal carcinoma in situ and other papillary breast neoplasms. Recurrent chromosomal changes include gains of chromosome arms 1q and 8q, loss of 16q, and amplification of 17q12 containing the ERBB2 gene, which contributes to HER2 overexpression in a subset of lesions.

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		P	No	Gain of chromosome 1q is frequently observed in early breast neoplasia including DCIS and contributes to tumor progression.
8	Gain	8q24	MYC	P	No	Gain of 8q results in MYC activation and increased cell proliferation in breast tumors.
11	Gain	11q13	CCND1	P	No	Amplification of CCND1 leads to dysregulated cell cycle progression and has been reported in breast tumors.
13	Loss	13q14	RB1	P	No	Loss of RB1 contributes to cell cycle dysregulation in breast cancer.
16	Loss	16q	CDH1	P	No	Loss of chromosome arm 16q is commonly associated with low-grade breast tumors and ductal carcinoma in situ.
17	Amp	17q12	ERBB2	D, P, T	Yes (NCCN)	Amplification of ERBB2 results in HER2 overexpression and may guide targeted therapy decisions in breast cancer.

Characteristic Chromosomal or Other Global Mutational Patterns

Breast neoplasms including ductal carcinoma in situ frequently demonstrate chromosomal instability and aneuploidy, which contribute to copy-number alterations and genomic heterogeneity. In some tumors, defects in DNA repair pathways such as homologous recombination also contribute to mutational accumulation.

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
Chromosomal instability (CIN)	Accumulation of chromosomal gains and losses due to defects in mitotic segregation and DNA repair pathways	Common (>20%)	P	No	Chromosomal instability contributes to genomic heterogeneity and tumor evolution in breast tumors.
Aneuploidy	Abnormal chromosome numbers caused by chromosomal missegregation during cell division	Common (>20%)	P	No	Aneuploidy is frequently observed in breast tumors and is associated with tumor progression.
Homologous recombination deficiency	Homologous recombination deficiency	Rare (<5%)	P, T	Yes	HR deficiency may influence response to PARP inhibitor therapy in breast cancer; however, PARP inhibitor therapy is not applicable to in situ disease.

Gene Mutations (SNV/INDEL)

Breast tumors including ductal carcinoma in situ frequently harbor recurrent somatic mutations affecting pathways involved in cell proliferation, transcriptional regulation, and genomic stability. Commonly mutated genes include PIK3CA, TP53, and GATA3, among others. The mutational profile of papillary DCIS largely overlaps with other luminal-type breast neoplasms.

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
PIK3CA	Activating mutations	Oncogene	Common	T	Yes (NCCN)	Activates PI3K–AKT signaling pathway leading to increased cell growth and survival. Targeted therapy for invasive disease.
TP53	Inactivating mutations	TSG	Recurrent	P	Yes	Associated with genomic instability and aggressive tumor behavior
GATA3	Inactivating mutations	Other	Recurrent	P	No	Transcription factor regulating luminal cell differentiation in breast epithelium
ERBB2	Activating mutations, amplification	Oncogene	Recurrent	D, P, T	Yes (NCCN)	Drives HER2 signaling and may guide targeted therapy decisions.
MAP3K1	Inactivating mutations	TSG	Recurrent	P	No	Implicated in MAPK signaling and luminal breast cancer development.
CDH1	Inactivating mutations	TSG	Rare	P	Yes	Loss of E-cadherin disrupts cell adhesion and promotes tumor progression.

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

Epigenetic changes in breast tumor development include alterations in DNA methylation and chromatin remodeling. Hyper-methylation of tumor suppressor gene promoters, such as RASSF1A, CDH1, and BRCA1, in breast tumor samples has been documented and is believed to lead to gene silencing. Abnormalities in histone modification and chromatin remodeling are also known to affect gene expression patterns controlling cell proliferation and differentiation.

Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
PIK3CA, AKT1; activating mutations	PI3K-AKT-mTOR signaling	Increased cell proliferation and survival
PTEN; inactivating mutations	PI3K-AKT-mTOR signaling	Increased cell proliferation and survival
TP53; inactivating mutations	DNA damage response	Genomic instability and tumor progression
ERBB2; amplification or activating mutations	MAPK/PI3K signaling pathways	Enhanced growth signaling and tumorigenesis
GATA3; inactivating mutations	Estrogen signaling pathways	Altered luminal epithelial cell differentiation

Genetic Diagnostic Testing Methods

Genetic alterations in breast cancers can be identified through various molecular diagnostic methods. Next-generation sequencing (NGS) panel tests may be used to identify somatic mutations in PIK3CA, TP53, and GATA3 genes. Immunohistochemistry and in situ hybridization (ISH) are used to identify overexpression and amplification of the ERBB2 (HER2) gene, respectively. In addition, various PCR tests and comparative genomic hybridization (CGH) may be used to identify particular mutations and copy number variations.

Familial Forms

While the majority of breast tumors are considered to be sporadic, some cases are linked with hereditary cancer syndromes. Germline mutations in BRCA1 and BRCA2, PALB2, and CHEK2 are the most common genes associated with a hereditary predisposition to breast cancer. Additional susceptibility genes include TP53, which causes Li-Fraumeni syndrome, and PTEN, which causes Cowden syndrome.

Additional Information

Breast tumors are a diverse group of neoplastic disorders that vary in their molecular and histopathologic characteristics. Recent advances in genomic profiling have significantly enhanced our current understanding of tumor biology and have paved the way to develop novel therapeutic strategies. Molecular classification and genetic testing are assuming a significant role in diagnosis, prognosis, and treatment of breast cancer.

Links

WHO Classification of Tumours – Breast Tumours: https://publications.iarc.fr/581

cBioPortal for Cancer Genomics: https://www.cbioportal.org/

COSMIC – Catalogue of Somatic Mutations in Cancer: https://cancer.sanger.ac.uk/cosmic

The Cancer Genome Atlas (TCGA) Breast Cancer Dataset: https://www.cancer.gov/tcga

References

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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): *Citation of this Page: “Papillary ductal carcinoma in situ”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 04/12/2026, https://ccga.io/index.php/BRST5:Papillary ductal carcinoma in situ.