# Comprehensive molecular portraits of human breast tumours

Source: https://onco.cc/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/  
OnCo record `paper-tcga-breast-molecular-portraits-nature-2012` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Cancer Genome Atlas profiled hundreds of breast cancers on six platforms and found four main classes; the basal-like class, which is 80% triple-negative, carries TP53 mutation in 80%, frequent PTEN and RB1 loss, MYC and EGFR gains and looks molecularly like high-grade serous ovarian cancer.

## Summary

Primary breast cancers were analysed by copy-number arrays, DNA methylation, exome sequencing (510 with matched normals), mRNA arrays, microRNA sequencing and reverse-phase protein arrays. Only TP53, PIK3CA and GATA3 were mutated in more than 10% of all breast cancers. Basal-like tumours carried TP53 mutations in 80%, PIK3CA in 9%, PTEN mutation or loss in 35%, INPP4B loss in 30% and RB1 mutation or loss in 20%; PIK3CA (49%), KRAS (32%), BRAF (30%) and EGFR (23%) were amplified or gained but rarely mutated. Comparison with high-grade serous ovarian cancer showed many commonalities, indicating related aetiology and similar therapeutic opportunities. 80% of basal-like tumours were triple-negative.

Deposited as brca_tcga_pub on cBioPortal, with the 2018 PanCancer Atlas re-analysis as brca_tcga_pan_can_atlas_2018.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature
- Year: 2012
- DOI: 10.1038/nature11412
- Authors: Cancer Genome Atlas Network.
- Findings: Basal-like: TP53 mutation 80%, PTEN mutation or loss 35%, INPP4B loss 30%, RB1 mutation or loss 20%, PIK3CA mutation 9%.; Amplification rather than mutation of PIK3CA (49%), KRAS (32%), BRAF (30%) and EGFR (23%) in basal-like tumours.; Basal-like breast and high-grade serous ovarian cancers share their molecular profile; 80% of basal-like tumours are triple-negative.
- What it means: This is the reference frequency table for basal-like disease: it explains why PARP inhibitors and platinum, borrowed from ovarian cancer, work in TNBC, and why the PI3K pathway is broken by copy number rather than the hotspot mutations that drugs were designed against.
- Caveats: Basal-like is not identical to triple-negative: 10% of basal-like tumours are ER-positive and about a quarter of TNBCs are non-basal.; Frequencies are from 2012 pipelines; the 2018 PanCancer Atlas calls differ (PTEN deep deletion 21% and RB1 10.9% of 119 triple-negative samples on cBioPortal).

## Sources

- Cancer Genome Atlas Network, Nature 2012: comprehensive molecular portraits of human breast tumours: https://doi.org/10.1038/nature11412
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23000897/
- cBioPortal study brca_tcga_pub (TCGA, Nature 2012; 825 samples, 123 recorded ER-, PR- and HER2-negative, 84 of them exome-sequenced): https://www.cbioportal.org/study/summary?id=brca_tcga_pub
- cBioPortal study brca_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas; the same 123 triple-negative patients, all sequenced, 119 with copy number): https://www.cbioportal.org/study/summary?id=brca_tcga_pan_can_atlas_2018

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [High-grade serous ovarian cancer](https://onco.cc/cancers/high-grade-serous-ovarian-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/), [PTEN](https://onco.cc/targets/pten/), [RB1](https://onco.cc/targets/rb1/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [MYC](https://onco.cc/pathways/myc/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- terms: [PAM50 / intrinsic subtypes](https://onco.cc/terms/pam50/)
- people: [Charles M. Perou](https://onco.cc/people/charles-perou/)
- journals: [Nature](https://onco.cc/journals/nature/)
- biomarkers: [PTEN alteration (sequencing) and PTEN loss (IHC)](https://onco.cc/biomarkers/pten-alteration/)

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