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Updated: Sep 20, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Classification of triple negative breast cancer by epithelial mesenchymal transition and the tumor immune
Francesc Font-Clos1,2, Stefano Zapperi1,2,3, Caterina A M La Porta4,5,6
1Center for Complexity and Biosystems, University of Milan, via Celoria 16, 20133, Milano, Italy.
Abstract:
Triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancers and differs from other invasive breast cancer types because it grows and spreads rapidly, it has limited treatment options and typically worse prognosis. Since TNBC does not express estrogen or progesterone receptors and little or no human epidermal growth factor receptor (HER2) proteins are present, hormone therapy and drugs targeting HER2 are not helpful, leaving chemotherapy only as the main systemic treatment option. In this context, it would be important to find molecular signatures able to stratify patients into high and low risk groups. This would allow oncologists to suggest the best therapeutic strategy in a personalized way, avoiding unnecessary toxicity and reducing the high costs of treatment. Here we compare two independent patient stratification strategies for TNBC based on gene expression data: The first is focusing on the epithelial mesenchymal transition (EMT) and the second on the tumor immune microenvironment. Our results show that the two stratification strategies are not directly related, suggesting that the aggressiveness of the tumor can be due to a multitude of unrelated factors. In particular, the EMT stratification is able to identify a high-risk population with high immune markers that is, however, not properly classified by the tumor immune microenvironment based strategy.
Insights
Two gene expression strategies for triple-negative breast cancer (TNBC) risk stratification were compared. The epithelial mesenchymal transition (EMT) approach identified high-risk patients with immune markers missed by the tumor immune microenvironment strategy.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Triple-negative breast cancer (TNBC) comprises 15-20% of breast cancers, characterized by rapid progression, limited treatments, and poor prognosis.
- TNBC lacks estrogen/progesterone receptors and HER2 expression, rendering hormone therapy and HER2-targeted drugs ineffective, thus relying primarily on chemotherapy.
- Identifying molecular signatures for risk stratification is crucial for personalized treatment strategies in TNBC, aiming to reduce toxicity and healthcare costs.
Purpose of the Study:
- To compare two independent gene expression-based patient stratification strategies for TNBC.
- To evaluate the effectiveness of epithelial mesenchymal transition (EMT) and tumor immune microenvironment (TME) signatures in identifying high-risk TNBC patients.
- To determine the relationship between EMT and TME stratification strategies.
Main Methods:
- Analysis of gene expression data from independent patient cohorts.
- Application of two distinct stratification strategies: one based on EMT markers and another on TME components.
- Comparative analysis of patient classifications generated by both strategies.
Main Results:
- The EMT and TME stratification strategies are not directly correlated.
- The EMT strategy identified a high-risk subgroup of TNBC patients who also exhibit high immune markers.
- This high-risk, immune-marker-positive subgroup was not accurately classified by the TME-based strategy.
Conclusions:
- Tumor aggressiveness in TNBC may stem from multiple, independent molecular factors.
- The EMT pathway plays a significant role in identifying aggressive TNBC phenotypes, even those with immune cell infiltration.
- Current TME-based stratification may overlook aggressive TNBC cases identified through EMT markers, highlighting the need for multifaceted approaches in risk assessment.
