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Breast Cancer Research
Published in: Breast Cancer Research 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications

Authors: Pascal Jézéquel, Olivier Kerdraon, Hubert Hondermarck, Catherine Guérin-Charbonnel, Hamza Lasla, Wilfried Gouraud, Jean-Luc Canon, Andrea Gombos, Florence Dalenc, Suzette Delaloge, Jérôme Lemonnier, Delphine Loussouarn, Véronique Verrièle, Mario Campone

Published in: Breast Cancer Research | Issue 1/2019

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Abstract

Background

Heterogeneity and lack of targeted therapies represent the two main impediments to precision treatment of triple-negative breast cancer (TNBC), and therefore, molecular subtyping and identification of therapeutic pathways are required to optimize medical care. The aim of the present study was to define robust TNBC subtypes with clinical relevance.

Methods

Gene expression profiling by means of DNA chips was conducted in an internal TNBC cohort composed of 238 patients. In addition, external data (n = 257), obtained by using the same DNA chip, were used for validation. Fuzzy clustering was followed by functional annotation of the clusters. Immunohistochemistry was used to confirm transcriptomics results: CD138 and CD20 were used to test for plasma cell and B lymphocyte infiltrations, respectively; MECA79 and CD31 for tertiary lymphoid structures; and UCHL1/PGP9.5 and S100 for neurogenesis.

Results

We identified three molecular clusters within TNBC: one molecular apocrine (C1) and two basal-like-enriched (C2 and C3). C2 presented pro-tumorigenic immune response (immune suppressive), high neurogenesis (nerve infiltration), and high biological aggressiveness. In contrast, C3 exhibited adaptive immune response associated with complete B cell differentiation that occurs in tertiary lymphoid structures, and immune checkpoint upregulation. External cohort subtyping by means of the same approach proved the robustness of these results. Furthermore, plasma cell and B lymphocyte infiltrates, tertiary lymphoid structures, and neurogenesis were validated at the protein levels by means of histological evaluation and immunohistochemistry.

Conclusion

Our work showed that TNBC can be subcategorized in three different subtypes characterized by marked biological features, some of which could be targeted by specific therapies.
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Metadata
Title
Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications
Authors
Pascal Jézéquel
Olivier Kerdraon
Hubert Hondermarck
Catherine Guérin-Charbonnel
Hamza Lasla
Wilfried Gouraud
Jean-Luc Canon
Andrea Gombos
Florence Dalenc
Suzette Delaloge
Jérôme Lemonnier
Delphine Loussouarn
Véronique Verrièle
Mario Campone
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2019
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1148-6

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