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Updated: May 28, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Molecular heterogeneity of triple-negative breast cancer and its clinical implications
Sheeba Irshad1, Paul Ellis, Andrew Tutt
1Breakthrough Breast Cancer Research Unit, Research Oncology, Kings College London School of Medicine, Kings Health Partners AHSC, London, UK.
Purpose Of Review:
Triple-negative breast cancer (TNBC) is defined by a lack of expression of hormone receptors, oestrogen and progesterone, as well as human epidermal factor receptor 2. This review focuses on the increasing understanding of the molecular heterogeneity of TNBC subtypes and the therapeutic implications of this subclassification.
Recent Findings:
Emerging evidence clearly indicates that TNBC is a heterogeneous disease with varying prognosis according to clinical, pathological and genetic factors. Some distinct histological special types within this clinically defined collection of entities have been shown to have a particularly good prognosis (e.g. medullary carcinomas), and others very poor outcome (e.g. metaplastic carcinomas), whereas the broader immunohistochemically defined 'core-basal-like' or gene expression defined 'basal' groups generally have a poor prognosis. This molecular subclassification has implicated several biological processes as potential therapeutic targets: the DNA damage response, drivers of deregulated proliferation, angiogenesis, epithelial-mesenchymal transition and immune deregulation.
Summary:
Molecular stratification of these prognostic groups has been critical in identifying novel therapeutic targets for future drug development. The development of poly-(ADP)ribose polymerase inhibitors for BRCA1-mutation carriers with TNBC has led the ongoing efforts to translate fundamental biological insights into improved therapies for a difficult-to-treat breast cancer subgroup.
Insights
Triple-negative breast cancer (TNBC) is a complex disease with diverse subtypes. Understanding this molecular heterogeneity is key to developing targeted therapies for this challenging breast cancer subgroup.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors.
- TNBC is characterized by significant molecular heterogeneity, impacting prognosis and treatment strategies.
Purpose of the Study:
- To review the molecular heterogeneity of TNBC subtypes.
- To explore the therapeutic implications of TNBC subclassification.
Main Methods:
- Review of emerging evidence on TNBC heterogeneity.
- Analysis of clinical, pathological, and genetic factors influencing prognosis.
- Identification of biological processes as potential therapeutic targets.
Main Results:
- TNBC exhibits significant heterogeneity with varying prognoses based on subtype.
- Specific histological types (e.g., medullary, metaplastic) show distinct outcomes.
- Molecular subclassification highlights targets like DNA damage response, proliferation, angiogenesis, EMT, and immune deregulation.
Conclusions:
- Molecular stratification is crucial for identifying novel therapeutic targets in TNBC.
- Poly-(ADP)ribose polymerase inhibitors represent a successful translation of biological insights for BRCA1-mutation carriers with TNBC.
