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Updated: Oct 15, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Functional Proteomic Profiling of Triple-Negative Breast Cancer
Irina Gromova1, Jaime A Espinoza2, Morten Grauslund3
1Genome Integrity Unit, Danish Cancer Society Research Center, Cancer Proteomics Group, DK-2100 Copenhagen, Denmark.
Abstract:
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples. We performed supervised and unsupervised approaches to proteomic data analysis to identify groups of samples sharing common characteristics that could be amenable to existing therapies. We found the heterogenous activation of multiple pathways, with PI3 K/AKT/mTOR signaling being the most common event. Some specific individualized therapeutic possibilities include the expression of oncogenic KIT in association with cytokeratin 15 and Erk1/2 positive tumors, both of which may have clinical value.
Insights
Triple-negative breast cancer (TNBC) exhibits diverse signaling pathways, with PI3K/AKT/mTOR activation being most common. Proteomic profiling reveals potential targeted therapies for specific TNBC subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and HER2 expression.
- Conventional chemotherapy is the primary treatment for TNBC due to its receptor-negative status.
Purpose of the Study:
- To quantitatively profile signaling intermediates in TNBC.
- To identify TNBC subtypes amenable to targeted therapies.
Main Methods:
- Utilized reverse phase protein array (RPPA) and immunohistochemistry.
- Analyzed proteomic data using supervised and unsupervised methods on 44 TNBC samples.
- Profiled activation states of 84 signaling intermediates and phosphoproteins.
Main Results:
- Identified heterogeneous activation across multiple signaling pathways in TNBC.
- PI3K/AKT/mTOR signaling was the most frequently observed activated pathway.
- Found potential therapeutic targets including oncogenic KIT, cytokeratin 15, and Erk1/2 expression.
Conclusions:
- TNBC is characterized by diverse signaling pathway activation.
- Specific molecular profiles may guide individualized therapeutic strategies for TNBC patients.
- Further research into targeted therapies based on identified signaling pathways is warranted.
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