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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
Giampaolo Bianchini1, Justin M Balko2,3, Ingrid A Mayer2
1Department of Medical Oncology, IRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132 Italy.
Abstract:
Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.
Insights
Triple-negative breast cancer (TNBC) lacks targeted therapies. Recent
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is aggressive, lacking targeted therapies, necessitating novel treatment strategies.
- Tumor heterogeneity and molecular alterations present challenges and opportunities for TNBC treatment.
- Chemotherapy remains the primary systemic treatment, but improved outcomes are needed.
Purpose of the Study:
- To review key molecular findings in TNBC over the past decade.
- To identify promising therapeutic opportunities based on molecular insights.
- To discuss the potential of immunotherapy for TNBC patients.
Main Methods:
- Comprehensive literature review of TNBC research from the last 10 years.
- Analysis of 'omics' data to identify actionable molecular targets.
- Evaluation of clinical trial data for immunotherapy in advanced TNBC.
Main Results:
- TNBC exhibits significant heterogeneity, with actionable targets like BRCA1/2 mutations, 'BRCAness,' androgen receptor, and rare genomic alterations identified.
- High tumor-infiltrating lymphocytes correlate with reduced relapse risk and better chemotherapy response.
- Immunotherapy with checkpoint inhibitors shows promise in advanced TNBC.
Conclusions:
- Molecular profiling is crucial for understanding TNBC heterogeneity and identifying personalized treatment strategies.
- Targeting identified molecular alterations and leveraging the tumor immune microenvironment offer new therapeutic avenues.
- Immunotherapy represents a promising frontier for improving outcomes in TNBC patients.
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