Invasive Breast Carcinoma (BRCA)

Overview

OncoTree code for invasive breast carcinoma.

Cohorts in the corpus

  • msk_chord_2024 — 5,368 breast cancer patients at MSK in the MSK-CHORD clinicogenomic harmonized real-world dataset PMID:39506116.
  • BT474 (HER2+, BRCA cell line): preclinical ADC radiosensitization model; T-MMAE bound BT474 receptor-selectively and arrested cells in G2/M at 2–5 nM. PMID:27698471
  • csf_msk_2024 — Breast cancer was the second most common primary cancer type in the MSK CSF ctDNA cohort (n=150 patients) PMID:39289779.

Recurrent alterations

  • Included in pan-cancer pathway and metastasis analyses using MSK-IMPACT PMID:39506116.
  • PIK3CA p.E545K common in breast cancer CSF ctDNA samples PMID:39289779.
  • ERBB2 mutations and amplification detected in breast cancer CSF ctDNA PMID:39289779.
  • ERBB2 (HER2) surface expression in BT474 (HER2+) cells enables receptor-restricted T-MMAE/T-DM1 radiosensitization; ado-trastuzumab emtansine (T-DM1) is FDA-approved for HER2+ metastatic breast cancer and was proposed for clinical evaluation with radiotherapy in HER2+ locally advanced disease. PMID:27698471
  • TP53 was the most frequently altered gene across all tumor types in the CSF ctDNA cohort (49% of ctDNA-positive samples), including breast cancer PMID:39289779.
  • Breast cancer patients with BRCA1/2 mutations demonstrated improved outcomes with PARP inhibitor therapy in a prospective study PMID:36585450
  • Whole-exome sequencing of 102 breast cancer samples identified recurrent SF3B1 mutations and widespread splicing alterations, providing new insight into BRCA mutational landscape PMID:22158541
  • WGS of 65 breast tumors (BCCRC cohort) characterized structural rearrangements and somatic mutations in invasive breast carcinoma PMID:22495314
  • METABRIC study profiled ~2,000 breast tumors identifying 10 integrative clusters (IntClust1–10) with distinct copy-number and expression signatures in invasive breast carcinoma PMID:22522925
  • Whole-exome sequencing of 100 breast cancer tumors (Sanger cohort, brca_sanger) identified ~40 driver genes including PIK3CA, TP53, and CDH1 with recurrent somatic mutations PMID:22722201
  • WES/WGS of 103 breast tumors (Broad cohort, brca_broad) identified PIK3CA as the most frequently mutated gene and discovered MAGI3-AKT3 fusion kinase as a novel driver PMID:22722202
  • Comprehensive genomic characterization of 510 breast tumors identified four molecular subtypes (Luminal A/B, HER2-enriched, Basal-like) with distinct mutation profiles PMID:23000897
  • Generation of 30 breast cancer PDX lines from 55 BRCA patients showed universal clonal selection at engraftment in all 15 WGS-characterized series, with minor (<5%) clones frequently expanding to dominance; replicate transplants produced highly concordant clonal dynamics (median Pearson r 0.91-0.94), establishing deterministic clonal fitness as a key property of BRCA PDX models PMID:25470049.
  • Adenoid cystic breast carcinoma (ACBC) is a rare subtype of invasive breast carcinoma; study characterized its genomic landscape including MYB-NFIB fusions and copy number alterations PMID:26095796
  • Large-scale multi-platform analysis of invasive breast carcinoma identified distinct molecular subtypes including luminal A, luminal B, HER2-enriched, and basal-like, with comprehensive genomic characterization across 825 samples PMID:26437033
  • Comparative genomic profiling of invasive breast carcinoma subtypes identified recurrent alterations in PIK3CA, TP53, and CDH1 with subtype-specific patterns across IDC and ILC PMID:26451490
  • Targeted sequencing of 173 genes in 2,433 primary breast tumours (METABRIC cohort) identified 40 Mut-driver genes; top altered genes: PIK3CA (40.1%), TP53 (35.4%), KMT2C (11.4%), GATA3 (11.1%); 45.2% of tumours harboured an Akt-pathway mutation; PIK3CA prognostic value in ER+ disease depends on IntClust background (poor outcome in IntClusts 1, 2, 9 only); CDH1 inactivating mutations in 52.6% of lobular carcinomas PMID:27161491
  • WES on 216 metastatic breast cancer (mBC) tumor-blood pairs from French SAFIR01/SAFIR02/SHIVA/MOSCATO trials: ESR1 mutations in 14% and amplification in 6% of HR+/HER2- mBC (combined 19%), emerging as metastasis-specific drivers; RB1 loss-of-function in 6% of HR+/HER2- mBC (CDK4i resistance marker); TSC1/TSC2 combined 6.3% of HR+/HER2- mBC vs 0.7% primary (p=0.0004); PALB2 somatic 4% of mBC vs 0.1% of primary; APOBEC signatures 2+13 contributed 58.8% vs 31.9% of mutations in HR+ primary; 8-gene metastatic-enrichment signature carried 2-fold higher death hazard (HR=1.97, p=0.001) PMID:28027327
  • In the MSK-IMPACT pan-cancer cohort, ESR1 hotspot mutations were found in 11% of BRCA (vs 4% in TCGA), almost exclusively in post-hormone-therapy metastases, consistent with endocrine-resistance; 57% of BRCA patients harbored an OncoKB-actionable alteration (3rd highest after GIST and thyroid). PMID:28481359
  • MET500 metastatic cohort: breast carcinoma was the second most common cancer type (91/500, 18.2%); BRCA1/BRCA2 germline pathogenic variants were significantly enriched vs ExAC controls (BRCA1 n=5, BRCA2 n=9); MImmScore immune analysis showed metastatic breast tumors have low immune infiltration similar to primary disease. PMID:28783718
  • In the SUMMIT basket trial of neratinib for ERBB2/ERBB3-mutant solid tumors, HER2-mutant non-amplified invasive breast carcinoma met its pre-specified efficacy endpoint with ORR8 32% (8/25, 95% CI 15-54%) across ER+ and ER- subtypes and across extracellular and kinase domain mutations PMID:29420467
  • MC3 pan-cancer mutation-calling project (10,510 TCGA pairs) included BRCA; concordance with the legacy PanCan12 MAF exceeded 90% PMID:29596782
  • Pan-cancer fusion study (9,624 TCGA samples) identified 16 ESR1 fusions across 5 cancer types, 9 in BRCA (8 luminal A/B), with strict mutual exclusivity with ESR1 point mutations and elevated ESR1 expression in fusion-positive samples; ERBB2 fusions also detected with HPV-integration proximity PMID:29617662
  • Pan-cancer aneuploidy study placed BRCA in the ‘epithelial cluster’ defined by 1q gain (alongside LUAD and HCC); chr_3p-loss/3q-gain squamous signature was absent in BRCA; TSG-partner fusion under-expression ranged 3% (BRCA) to 38% (PCPG) PMID:29622463

Subtypes

Therapeutic landscape

  • ATLAS RNA-expression classifier achieved 97.1% lineage accuracy and 91.4% site-of-origin accuracy; breast was included in the 22-class site classifier and shows prognostic value of de-differentiation score (HR 0.41, P=0.002) PMID:27634761.
  • ctDNA detection was independently associated with VTE risk in breast cancer patients (13% of discovery cohort); anticoagulation was associated with lower VTE rates in ctDNA-positive patients (adjusted HR=0.50) PMID:39147831.
  • NLP-augmented machine learning models incorporating sites of disease improved overall-survival prediction over stage- or genomics-only models in breast cancer PMID:39506116.
  • APOBEC mutational signatures identified in CSF ctDNA from breast cancer samples, aiding in determining the primary tumor site PMID:39289779.
  • CSF ctDNA positivity was associated with a three-fold increased risk of death across all tumor types (HR 3.23, 95% CI 2.58-4.05, p < 0.001) PMID:39289779.
  • ado-trastuzumab emtansine (T-DM1) + IR proposed as a radiosensitization strategy for HER2+ locally advanced breast cancer given T-DM1’s existing FDA approval and preclinical tumor-control data in HER2+ xenografts; no breast-specific clinical data reported. PMID:27698471

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29420467

This page was processed by entity-page-writer on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15. - PMID:29622463

This page was processed by wiki-cli on 2026-05-15.