# Mesenchymal triple-negative breast cancer (M)

Source: https://onco.cc/cancers/tnbc-mesenchymal/  
OnCo record `tnbc-mesenchymal` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Mesenchymal triple-negative breast cancers have switched on the programme cells use to migrate (epithelial-to-mesenchymal transition). They overlap with claudin-low and metaplastic tumours, respond to chemotherapy less well than basal-like 1 tumours, and are the subtype the parent page names as resisting every drug class.

## Summary

The mesenchymal (M) and mesenchymal stem-like (MSL) subtypes were enriched for epithelial-to-mesenchymal transition and growth factor pathway genes, and their cell lines responded to a PI3K/mTOR inhibitor and to dasatinib in the defining study (Lehmann 2011). In the 2016 refinement the stem-like signal proved to come from tumour-associated stromal cells, leaving M as the tumour-intrinsic mesenchymal subtype (Lehmann 2016). Burstein's mesenchymal (MES) subtype carries growth factor receptor targets (PDGFR alpha, c-KIT) (Burstein 2015). The claudin-low intrinsic subtype describes much of the same biology from the whole-breast-cancer side: low luminal differentiation markers, high epithelial-to-mesenchymal transition and stem-cell features, mostly triple-negative invasive carcinomas with frequent metaplastic and medullary differentiation, and a preoperative chemotherapy response between basal-like and luminal tumours (Prat 2010); a 2020 re-analysis found claudin-low is better understood as a phenotype with low genomic instability, low proliferation and high immune and stromal infiltration that can overlay any intrinsic subtype (Fougner 2020). Metaplastic carcinoma, the histological type most often mesenchymal, is on its own page.

A research classification by gene expression (Lehmann 2011, refined 2016), not a test the NHS runs; treatment follows the triple-negative rows on the parent page.

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: M subtype; Mesenchymal TNBC; MES subtype (Burstein); Claudin-low triple-negative breast cancer (overlapping phenotype)
- Tags: breast; tnbc; subtype-page
- Group: breast
- Burden: One of the four tumour-intrinsic triple-negative subtypes; overlaps the claudin-low phenotype and the metaplastic histological type.
- Subtypes: Claudin-low phenotype (low luminal markers, epithelial-to-mesenchymal transition, stem-cell features); Metaplastic carcinoma with spindle cell or matrix-producing components (own page)
- Biomarkers: Epithelial-to-mesenchymal transition gene expression (research); Low claudin 3, 4 and 7 and E-cadherin expression (claudin-low); PDGFR alpha and c-KIT (Burstein MES)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/tnbc-mesenchymal/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/tnbc-mesenchymal/#overview
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/tnbc-mesenchymal/#what-it-is [2 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/tnbc-mesenchymal/#finding-it [3 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/tnbc-mesenchymal/#treating-it [1 setting]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/tnbc-mesenchymal/#evidence [1 trial]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/tnbc-mesenchymal/#science [1 target, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/tnbc-mesenchymal/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/tnbc-mesenchymal/#living-with-it [9 questions, 3 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/tnbc-mesenchymal/coming/ [1 medicine]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/tnbc-mesenchymal/data/ [9 connected records]

## Standard of care

- Stage II to III and metastatic: As for triple-negative disease; no mesenchymal-specific treatment is approved. PI3K/mTOR inhibitors and dasatinib were active in cell lines only. ([KEYNOTE-522](https://onco.cc/trials/keynote-522/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Triple-negative_breast_cancer
- Lehmann, J Clin Invest 2011: identification of human triple-negative breast cancer subtypes (BL1, BL2, IM, M, MSL, LAR): https://doi.org/10.1172/jci45014
- Lehmann, PLoS One 2016: refinement of triple-negative breast cancer molecular subtypes to four (TNBCtype-4): https://doi.org/10.1371/journal.pone.0157368
- Burstein, Clin Cancer Res 2015: four triple-negative subtypes (LAR, MES, BLIS, BLIA) with distinct prognoses: https://doi.org/10.1158/1078-0432.ccr-14-0432
- Prat, Breast Cancer Res 2010: phenotypic and molecular characterisation of the claudin-low intrinsic subtype: https://doi.org/10.1186/bcr2635
- Fougner, Nat Commun 2020: re-definition of claudin-low as a breast cancer phenotype: https://doi.org/10.1038/s41467-020-15574-5

## Connected records

- cancers: [Basal-like 2 triple-negative breast cancer (BL2)](https://onco.cc/cancers/tnbc-basal-like-2/), [Mesenchymal stem-like triple-negative breast cancer (MSL)](https://onco.cc/cancers/tnbc-mesenchymal-stem-like/), [Metaplastic breast carcinoma](https://onco.cc/cancers/metaplastic-breast-carcinoma/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- terms: [Basal-like breast cancer](https://onco.cc/terms/basal-like/), [Claudin-low breast cancer](https://onco.cc/terms/claudin-low/)
- trials: [KEYNOTE-522](https://onco.cc/trials/keynote-522/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)

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JSON: https://onco.cc/api/v1/entities/tnbc-mesenchymal.json