Related Experiment Video
Updated: Jan 24, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications
Pascal Jézéquel1,2,3, Olivier Kerdraon4, Hubert Hondermarck5
1Département de Biopathologie, Unité Mixte de Génomique du Cancer, Institut de Cancérologie de l'Ouest - site René Gauducheau, Bd Jacques Monod, 44805, Saint Herblain Cedex, France. Pascal.jezequel@ico.unicancer.fr.
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.
Insights
Researchers identified three distinct molecular subtypes of triple-negative breast cancer (TNBC). These subtypes, characterized by unique biological features, offer potential targets for developing more precise and effective TNBC therapies.
Area of Science:
- Genomics and Molecular Biology
- Oncology
- Immunology
Background:
- Triple-negative breast cancer (TNBC) exhibits significant heterogeneity, hindering precision treatment.
- Lack of targeted therapies necessitates molecular subtyping for optimized medical care.
- Identifying clinically relevant TNBC subtypes is crucial for advancing treatment strategies.
Purpose of the Study:
- To define robust molecular subtypes of triple-negative breast cancer (TNBC) with clinical relevance.
- To identify distinct biological features within TNBC subtypes for potential therapeutic targeting.
Main Methods:
- Gene expression profiling using DNA chips on an internal TNBC cohort (n=238) and an external validation cohort (n=257).
- Fuzzy clustering for molecular subtyping, followed by functional annotation.
- Immunohistochemistry to validate transcriptomic findings, including immune cell infiltrates, tertiary lymphoid structures, and neurogenesis markers.
Main Results:
- Three molecular TNBC subtypes were identified: molecular apocrine (C1) and two basal-like-enriched (C2, C3).
- Subtype C2 showed immune suppressive characteristics, high neurogenesis, and aggressive tumor behavior.
- Subtype C3 exhibited adaptive immune responses, B cell differentiation within tertiary lymphoid structures, and immune checkpoint upregulation. These findings were validated at the protein level.
Conclusions:
- TNBC can be subcategorized into three distinct subtypes based on significant biological features.
- These identified subtypes present opportunities for developing targeted therapies for TNBC.
- The molecular subtyping approach provides a foundation for more personalized treatment strategies in TNBC.
Related Concept Videos
01:06Scalar and Vector Triple Products
The scalar triple product is the dot product of a vector with the cross product of two vectors....
01:23Negative Regulator Molecules
01:31Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
01:21The Resting Membrane Potential
00:58Positive, Negative, and Zero Work