Related Experiment Video
Updated: Mar 20, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
The Evolution of Triple-Negative Breast Cancer: From Biology to Novel Therapeutics
Carey K Anders1, Vandana Abramson1, Tira Tan1
1From the Department of Medicine, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, TN; Department of Medicine, National Cancer Center Singapore, Singapore; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Abstract:
Triple-negative breast cancer (TNBC) is clinically defined as lacking expression of the estrogen receptor (ER), progesterone receptor (ER), and HER2. Historically, TNBC has been characterized by an aggressive natural history and worse disease-specific outcomes compared with other breast cancer subtypes. The advent of next-generation sequencing (NGS) has allowed for the dissection of TNBC into molecular subtypes (i.e., basal-like, claudin-low). Within TNBC, several subtypes have emerged as "immune-activated," consistently illustrating better disease outcome. In addition, NGS has revealed a host of molecular features characteristic of TNBC, including high rates of TP53 mutations, PI3K and MEK pathway activation, and genetic similarities to serous ovarian cancers, including inactivation of the BRCA pathway. Identified genetic vulnerabilities of TNBC have led to promising therapeutic approaches, including DNA-damaging agents (i.e., platinum salts and PARP inhibitors), as well as immunotherapy. Platinum salts are routinely incorporated into the treatment of metastatic TNBC; however, best outcomes are observed among those with deficiencies in the BRCA pathway. Although the incorporation of platinum in the neoadjuvant care of patients with TNBC yields higher pathologic complete response (pCR) rates, the impact on longer-term outcome is less clear. The presence of immune infiltrate in TNBC has shown both a predictive and prognostic role. Checkpoint inhibitors, including PD-1 and PD-L1 inhibitors, are under investigation in the setting of metastatic TNBC and have shown responses in initial clinical trials. Finally, matching emerging therapeutic strategies to optimal subtype of TNBC is of utmost importance as we design future research strategies to improve patient outcome.
Insights
Triple-negative breast cancer (TNBC) is aggressive, but molecular subtypes offer new therapeutic targets. Immune-activated TNBC subtypes show better outcomes, guiding personalized treatment strategies for improved patient survival.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR), and HER2 expression.
- TNBC is known for its aggressive nature and poorer outcomes compared to other breast cancer subtypes.
- Next-generation sequencing (NGS) has enabled the classification of TNBC into distinct molecular subtypes, such as basal-like and claudin-low.
Purpose of the Study:
- To explore the molecular landscape of TNBC using NGS.
- To identify therapeutic vulnerabilities and promising treatment strategies for TNBC.
- To investigate the role of immune infiltrate and its impact on TNBC outcomes.
Main Methods:
- Utilized Next-Generation Sequencing (NGS) for molecular subtyping of TNBC.
- Analyzed genetic features including TP53 mutations, PI3K/MEK pathway activation, and BRCA pathway inactivation.
- Reviewed clinical data on treatment responses to DNA-damaging agents and immunotherapies.
Main Results:
- Identified 'immune-activated' TNBC subtypes associated with improved disease outcomes.
- Revealed genetic similarities between TNBC and serous ovarian cancers, including BRCA pathway inactivation.
- Demonstrated that platinum salts and PARP inhibitors show efficacy, particularly in BRCA-deficient TNBC.
- Observed higher pathologic complete response (pCR) rates with neoadjuvant platinum, though long-term impact requires further study.
- Highlighted the predictive and prognostic significance of tumor immune infiltrate in TNBC.
Conclusions:
- Molecular subtyping of TNBC is crucial for understanding disease heterogeneity and guiding treatment.
- Targeting genetic vulnerabilities like BRCA pathway defects with platinum salts and PARP inhibitors shows promise.
- Immunotherapy, including PD-1/PD-L1 inhibitors, is a developing strategy for metastatic TNBC.
- Tailoring emerging therapies to specific TNBC molecular subtypes is essential for improving patient outcomes.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
02:56Treatment Resistent Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:56Treatment Resistant Cancers
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...