Related Experiment Video
Updated: May 5, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
The omics of triple-negative breast cancers
Hong Xu1, Peter Eirew, Sarah C Mullaly
1Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC;
Background:
Triple-negative breast cancers (TNBC) do not represent a single disease subgroup and are often aggressive breast cancers with poor prognoses. Unlike estrogen/progesterone receptor and HER2 (human epidermal growth factor receptor 2) breast cancers, which are responsive to targeted treatments, there is no effective targeted therapy for TNBC, although approximately 50% of patients respond to conventional chemotherapies, including taxanes, anthracyclines, cyclophosphamide, and platinum salts.
Content:
Genomic studies have helped clarify some of the possible disease groupings that make up TNBC. We discuss the findings, including copy number-transcriptome analysis, whole genome sequencing, and exome sequencing, in terms of the biological properties and phenotypes that make up the constellation of TNBC. The relationships between subgroups defined by transcriptome and genome analysis are discussed.
Summary:
TNBC is not a uniform molecular or disease entity but a constellation of variably well-defined biological properties whose relationship to each other is not understood. There is good support for the existence of a basal expression subtype, p53 mutated, high-genomic instability subtype of TNBC. This should be considered a distinct TNBC subtype. Other subtypes with variable degrees of supporting evidence exist within the nonbasal/p53wt (wild-type p53) TNBC, including a group of TNBC with PI3K (phosphoinositide 3-kinase) pathway activation that have better overall prognosis than the basal TNBC. Consistent molecular phenotyping of TNBC by whole genome sequencing, transcriptomics, and functional studies with patient-derived tumor xenograft models will be essential components in clinical and biological studies as means of resolving this heterogeneity.
Insights
Triple-negative breast cancer (TNBC) is a diverse group of aggressive tumors lacking targeted therapies. Genomic and transcriptomic analyses reveal distinct subtypes, including a basal, p53-mutated type and a PI3K-activated type with a better prognosis.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies, unlike receptor-positive breast cancers.
- TNBC heterogeneity contributes to poor prognoses, necessitating a deeper understanding of its molecular underpinnings.
- Current treatments for TNBC include conventional chemotherapies, with variable patient response rates.
Purpose of the Study:
- To elucidate the molecular heterogeneity of TNBC by integrating genomic and transcriptomic data.
- To identify distinct biological subgroups within TNBC based on molecular profiles.
- To understand the relationships between different TNBC molecular subtypes.
Main Methods:
- Copy number-transcriptome analysis
- Whole genome sequencing
- Exome sequencing
- Analysis of biological properties and phenotypes
Main Results:
- TNBC is not a single entity but a constellation of molecularly diverse subtypes.
- Evidence supports a distinct basal expression subtype characterized by p53 mutation and high genomic instability.
- A non-basal subtype with PI3K pathway activation shows a better prognosis compared to basal TNBC.
Conclusions:
- Consistent molecular phenotyping using genomics, transcriptomics, and patient-derived xenografts is crucial for understanding TNBC heterogeneity.
- Identifying distinct TNBC subtypes is essential for developing targeted therapies and improving patient outcomes.
- Further research is needed to understand the relationships between identified TNBC subtypes.
