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Updated: Feb 11, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Update on the Treatment of Early-Stage Triple-Negative Breast Cancer
1Division of Medical Oncology, University of Kansas Medical Center, 2330 Shawnee Mission Pkwy, Westwood, KS, 66205, USA. psharma2@kumc.edu.
Opinion Statement:
Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.
Insights
Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies, necessitating new treatment strategies. Biomarkers like BRCA mutations and BRCAness show promise for identifying patients who may benefit from DNA-damaging agents and targeted therapies.
Area of Science:
- Oncology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) represents 15% of breast cancers and has poorer outcomes than other subtypes.
- Current treatment relies on chemotherapy, as targeted therapies are not yet approved for TNBC.
- The biological complexity of TNBC has historically challenged the development of novel treatments.
Purpose of the Study:
- To explore advancements in TNBC subclassification.
- To investigate novel systemic therapies, including targeted agents and cytotoxic drugs.
- To identify promising biomarkers for patient selection in clinical trials.
Main Methods:
- Review of recent advancements in TNBC subclassification.
- Analysis of investigational approaches including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors.
- Emphasis on molecular biomarker-driven patient selection for clinical trial design.
Main Results:
- TNBC exhibits genetic enrichment for germline BRCA mutations and somatic homologous recombination deficiencies (BRCAness).
- BRCA mutations and BRCAness are identified as potential biomarkers for susceptibility to DNA-damaging therapies.
- Multiple targeted approaches are under investigation for early-stage TNBC.
Conclusions:
- Advancements in TNBC subclassification are enabling the investigation of more effective systemic therapies.
- Germline BRCA mutations and BRCAness are key biomarkers indicating potential response to DNA-damaging agents.
- Personalized medicine approaches using molecular biomarkers are crucial for accelerating the development and application of new TNBC treatments.
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