# Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer

Source: https://onco.cc/key-papers/paper-burstein-tnbc-genomic-subtypes-ccr-2015/  
OnCo record `paper-burstein-tnbc-genomic-subtypes-ccr-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A 2015 Baylor study of 198 triple-negative tumours that found four stable subtypes, luminal androgen receptor, mesenchymal, basal-like immune-suppressed and basal-like immune-activated, with the immune-activated group faring best and the immune-suppressed worst.

## Summary

Burstein, Tsimelzon, Poage, Covington and colleagues profiled RNA and DNA in 198 triple-negative tumours (oestrogen receptor negativity defined as Allred score 2 or less, more than 50 percent cellularity; discovery 84, validation 114) collected at Baylor College of Medicine, with an external set of seven public studies for confirmation. Four subtypes were identified and confirmed: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immunosuppressed (BLIS) and basal-like immune-activated (BLIA). Prognosis was worst for BLIS and best for BLIA for both disease-free survival (p=0.042 and 0.041) and disease-specific survival (p=0.039 and 0.029). Copy number analysis separated LAR from the other three and suggested amplification drives expression in some cases (FGFR2 in BLIS). Candidate subtype-specific targets were androgen receptor and MUC1 (LAR), PDGF receptor A and c-Kit (MES), VTCN1 (BLIS) and Stat molecules and cytokines (BLIA).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Clinical Cancer Research
- Year: 2015
- DOI: 10.1158/1078-0432.CCR-14-0432
- Authors: Burstein MD, Tsimelzon A, Poage GM, et al.
- Findings: Four subtypes confirmed in 198 tumours and seven external studies: LAR, MES, BLIS, BLIA.; Disease-free survival worst for BLIS (p=0.042) and best for BLIA (p=0.041); disease-specific survival likewise (p=0.039 and 0.029).; Candidate targets: androgen receptor and MUC1; PDGFRA and c-Kit; VTCN1; Stat signalling.
- What it means: Independently arrived at the same partition as the refined Lehmann scheme and added the insight that immune activation within basal-like tumours separates good from poor prognosis, the biology immunotherapy would exploit three years later.
- Caveats: Single-institution discovery set.; Candidate targets are computational; VTCN1 (B7-H4) antibody-drug conjugates are only now in early trials.

## Sources

- Clin Cancer Res 2015: https://doi.org/10.1158/1078-0432.CCR-14-0432
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25208879/

## Connected records

- key papers: [Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies](https://onco.cc/key-papers/paper-lehmann-tnbc-subtypes-jci-2011/)
- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [B7-H4 (VTCN1)](https://onco.cc/targets/b7h4/), [FGFR2](https://onco.cc/targets/fgfr2/), [PDGFRB](https://onco.cc/targets/pdgfrb/)
- institutions: [Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine](https://onco.cc/institutions/baylor-duncan/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)

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