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Updated: May 5, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
New targets for triple-negative breast cancer
Christina I Herold1, Carey K Anders
1Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Abstract:
Triple-negative breast cancer (TNBC) lacks the three most commonly targeted receptors in human breast cancer--the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu--and it is associated with an aggressive natural history. More recently, TNBC has been further dissected into smaller, distinct subsets with unique molecular alterations and response to therapy. Large-scale genomic projects have yielded new knowledge about the molecular characteristics of TNBC, including similarities with high-grade serous ovarian cancers, suggesting a possible coordinated treatment algorithm for these malignancies. Moreover, translation of preclinical findings has led to clinical trials testing a plethora of targets and pathways in TNBC, which will be reviewed here; these include epidermal growth factor receptor (EGFR), angiogenesis, DNA repair capacity, epigenetic regulation, androgen receptor (AR) and folate receptor (FR) signaling, cell-cycle control, and cell survival. Given the complexity of TNBC biology and the lack of "traditional" therapeutic targets, the advancement of care for women with TNBC will require a true partnership between clinicians, translational investigators, and basic scientists.
Insights
Triple-negative breast cancer (TNBC) is aggressive and lacks common targets. Research is exploring new molecular subsets and therapeutic strategies for this complex disease.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression.
- TNBC exhibits an aggressive clinical course and has been molecularly subtyped, revealing distinct alterations.
- Genomic studies highlight similarities between TNBC and high-grade serous ovarian cancers, suggesting potential for coordinated treatment approaches.
Purpose of the Study:
- To review current knowledge on the molecular characteristics of TNBC.
- To discuss emerging therapeutic targets and pathways being investigated in clinical trials for TNBC.
- To emphasize the need for interdisciplinary collaboration in advancing TNBC care.
Main Methods:
- Review of large-scale genomic projects and preclinical findings in TNBC.
- Analysis of ongoing clinical trials targeting various pathways in TNBC.
- Synthesis of information on molecular alterations and therapeutic strategies.
Main Results:
- TNBC exhibits diverse molecular subsets with unique alterations.
- Potential therapeutic targets include EGFR, angiogenesis, DNA repair, epigenetics, AR, and FR signaling.
- Similarities with ovarian cancers suggest shared treatment strategies.
Conclusions:
- Advancing TNBC treatment requires understanding its complex biology and molecular heterogeneity.
- Targeting specific pathways and leveraging similarities with other cancers are key research directions.
- Multidisciplinary collaboration is crucial for improving outcomes for patients with TNBC.
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