Breast Invasive Ductal Carcinoma (IDC)

Overview

Breast Invasive Ductal Carcinoma (IDC) is the most common histologic subtype of invasive breast cancer, arising from the ductal epithelium of the breast. It sits at OncoTree level 3 under BRCA. IDC encompasses all four intrinsic molecular subtypes (Luminal A, Luminal B, HER2-enriched, Basal-like) and is the reference comparator for understanding the distinct molecular biology of rarer breast histologies such as invasive lobular carcinoma (ILC).

Cohorts in the corpus

  • brca_tcga_pub2015 — 490 IDC samples profiled by whole-exome sequencing, RNA-seq, miRNA-seq, copy number (SNP6), DNA methylation, and RPPA; constitutes the primary IDC cohort in the TCGA comprehensive breast study PMID:26451490.
  • brca_metabric — used as a validation cohort for transcriptional subtype survival analyses PMID:26451490.
  • brca_tcga_pub — cited for TP53/PIK3CA co-mutation cross-species comparisons in ER+ breast cancer modeling PMID:26437033.

Recurrent alterations

  • TP53 mutation: 44% of IDC vs 8% of ILC (q=1.9E-14); IDC-enriched, reflecting high Basal-like and HER2-enriched representation PMID:26451490.
  • PIK3CA mutation: 33% of IDC vs 48% of ILC; less frequent in IDC than ILC but present across all subtypes PMID:26451490.
  • GATA3 mutation: IDC-enriched in Luminal A comparison (20% LumA IDC vs 5% LumA ILC, q=0.003) PMID:26451490.
  • MYC focal amplification: IDC-enriched (27% IDC vs 6% ILC, q=7.42E-7) PMID:26451490.
  • CCNE1 focal amplification: IDC-enriched (7% IDC vs 0% ILC, q=0.01) PMID:26451490.
  • CDH1 mutation: 2% of IDC vs 63% of ILC (q=3.94E-53); E-cadherin loss is the defining molecular feature distinguishing ILC from IDC PMID:26451490.
  • Invasive ductal carcinoma histology was produced in rat models by combined NF1+TP53 Indel editing (uniformly invasive, moderately differentiated) and PIK3CA-H1047R+TP53 Indel editing (invasive with papillary features) PMID:26437033.
  • WES of 216 metastatic breast carcinomas (SAFIR01/SAFIR02/SHIVA/MOSCATO trials) encompassing predominantly IDC tumors: ESR1, RB1, PALB2, TSC1/TSC2, and APOBEC enrichments characterize the metastatic vs primary mutation landscape; all ESR1-mutant patients had received prior endocrine therapy PMID:28027327

Subtypes

  • Intrinsic subtypes (PAM50) in IDC: Luminal A 41%, with higher proportions of Luminal B, HER2-enriched, and Basal-like compared with ILC; IDC spans the full molecular spectrum PMID:26451490.
  • Mixed IDC/ILC cases (n=88) molecularly resolve into IDC-like (64/88) or ILC-like (24/88) by majority vote of three classifiers; CDH1 status is the dominant discriminating feature PMID:26451490.

Therapeutic landscape

  • PIK3CA+TP53 co-mutated IDC tumors show transcriptional concordance with rat Pik3caH1047R/Tp53Indel models (Fisher’s exact p<1×10^-14 for overlapping up-regulated genes), supporting cross-species translational relevance for endocrine and combination therapy studies PMID:26437033.
  • AKT pathway activity in IDC is subtype-dependent; LumA IDC has substantially lower pAKT than ILC, HER2-enriched, or Basal-like IDC PMID:26451490.

Sources

  • PMID:26451490 — Ciriello et al., Comprehensive molecular portraits of invasive lobular breast cancer, Cell 2015.
  • PMID:26437033 — Bu et al., Rat somatic genome editing enables ER+ breast cancer modeling, bioRxiv 2025.

This page was processed by crosslinker on 2026-05-14. - PMID:28027327

This page was processed by wiki-cli on 2026-05-14.