# Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection

Source: https://onco.cc/key-papers/paper-lehmann-tnbctype-4-refinement-plos-one-2016/  
OnCo record `paper-lehmann-tnbctype-4-refinement-plos-one-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The 2016 revision that cut the six triple-negative subtypes to four after showing the immune and stem-like signals came from surrounding cells, and found that response to standard chemotherapy before surgery ranged from 41 percent in basal-like 1 to 18 percent in basal-like 2.

## Summary

Lehmann, Jovanović, Chen, Estrada and colleagues used histopathological quantification and laser-capture microdissection to show that transcripts of the immunomodulatory and mesenchymal stem-like subtypes came from infiltrating lymphocytes and tumour-associated stromal cells, and refined the classification to four tumour-specific subtypes (TNBCtype-4: BL1, BL2, M and LAR) that differ in age at diagnosis, grade, local and distant progression and histopathology. Retrospective evaluation of more than 300 triple-negative patients across five public neoadjuvant chemotherapy data sets showed pathological complete response in 41 percent of BL1 (95 percent confidence interval 33 to 51), 18 percent of BL2 (9 to 28) and 29 percent of LAR (17 to 41) tumours.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: PLoS One
- Year: 2016
- DOI: 10.1371/journal.pone.0157368
- Authors: Lehmann BD, Jovanović B, Chen X, et al.
- Findings: Immunomodulatory and mesenchymal stem-like signals traced to infiltrating lymphocytes and stroma; subtypes reduced to BL1, BL2, M and LAR.; Pathological complete response to neoadjuvant chemotherapy: BL1 41 percent (95 percent CI 33 to 51), BL2 18 percent (9 to 28), LAR 29 percent (17 to 41).
- What it means: The first evidence that molecular subtype predicts chemotherapy response in triple-negative disease, and the origin of the observation that the immune signal in these tumours is real and measurable, which tumour-infiltrating lymphocyte scoring later turned into a prognostic tool.
- Caveats: Retrospective, pooled public data with heterogeneous regimens.; No prospective trial has yet assigned treatment by TNBCtype.

## Sources

- PLoS One 2016: https://doi.org/10.1371/journal.pone.0157368
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27310713/

## 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: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [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/)
- institutions: [Vanderbilt-Ingram Cancer Center](https://onco.cc/institutions/vanderbilt-ingram/)
- terms: [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Tumour-infiltrating lymphocytes (TILs)](https://onco.cc/terms/tils/)
- bottlenecks: [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- 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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