Breast Ductal Carcinoma In Situ (DCIS)

Overview

Breast Ductal Carcinoma In Situ (DCIS) is a pre-invasive neoplasm in which malignant epithelial cells proliferate within the ductal system of the breast without breaching the basement membrane. It sits at OncoTree level 2 under the BREAST parent node. DCIS represents a heterogeneous entity with variable risk of progression to invasive ductal carcinoma (IDC); understanding the molecular events that drive this transition is a central clinical question.

Cohorts in the corpus

  • brca_metabric and brca_tcga_pub include primary invasive breast tumors used as human comparators in modeling studies; DCIS-specific cohorts are referenced indirectly via the rat somatic editing platform PMID:26437033.

Recurrent alterations

  • NF1 Indel editing alone in rat mammary gland produced DCIS histology in 12/13 cases (92%) — all ER+/PR+/Ki67+, at a median 4-week latency — establishing Nf1 biallelic loss as sufficient to initiate DCIS-like lesions in a preclinical model PMID:26437033.
  • Addition of TP53 Indel to Nf1 loss converted the DCIS phenotype to invasive ductal carcinoma, implicating combined NF1/TP53 inactivation in the DCIS-to-invasive transition PMID:26437033.

Subtypes

  • DCIS produced in the Nf1Indel rat model is uniformly hormone-receptor-positive (ER+/PR+), mirroring the most common human DCIS subtype and distinct from the ER-negative metaplastic DCIS seen in mouse models under identical genetic editing PMID:26437033.

Therapeutic landscape

  • Nf1Indel DCIS rat tumors regressed completely under ovariectomy (3/3 rats) and fulvestrant (4/4 rats), supporting endocrine sensitivity of NF1-loss-driven ER+ DCIS PMID:26437033.

Sources

  • PMID:26437033 — Bu et al., Rat somatic genome editing enables ER+ breast cancer modeling, bioRxiv 2025.

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