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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
The clinical promise of immunotherapy in triple-negative breast cancer
Praveen Vikas1,2, Nicholas Borcherding2,3,4,5, Weizhou Zhang2,3,4,5
1Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, USA, praveen-vikas@uiowa.edu.
Abstract:
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poorer outcomes compared to other breast cancer subtypes. Contributing to the worse prognosis in TNBC is the higher rates of relapse and rapid progression after relapse. Advances in targeted therapeutics and conventional chemotherapy for TNBC have been stymied due to the lack of specific targets. Moreover, the responses to chemotherapy in TNBC lack durability, partially accounting for the higher rates of relapse. Immunotherapy, notably immune-checkpoint blockade, has shown to improve survival and maintain robust antitumor responses in both hematologic and solid malignancies. Unlike lung cancer, melanoma, and bladder cancer, most breast cancers are not inherently immunogenic and typically have low T cell infiltration. However, among breast cancer subtypes, TNBC is characterized by greater tumor immune infiltrate and higher degree of stromal and intratumoral tumor-infiltrating lymphocytes (TILs), a predictive marker for responses to immunotherapy. Moreover, in TNBC, the high number of stromal TILs is predictive of more favorable survival outcomes and response to chemotherapy. Immunotherapy is being extensively explored in TNBC and clinical trials are showing some promising results. This article focuses on the rationale for immunotherapy in TNBC, to explore and discuss preclinical data, results from early clinical trials, and to summarize some ongoing trials. We will also discuss the potential application of immunotherapy in TNBC from a clinician's perspective.
Insights
Triple-negative breast cancer (TNBC) immunotherapy shows promise due to higher tumor-infiltrating lymphocytes (TILs) in TNBC. This approach may improve outcomes for patients with this aggressive breast cancer subtype.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its heterogeneity, poor prognosis, and high relapse rates.
- Lack of specific molecular targets and durable responses to conventional therapies limit treatment efficacy in TNBC.
- TNBC exhibits greater tumor immune infiltrate, including tumor-infiltrating lymphocytes (TILs), which are associated with improved survival and response to immunotherapy.
Purpose of the Study:
- To explore the rationale for utilizing immunotherapy in TNBC.
- To review preclinical data and early clinical trial results for immunotherapy in TNBC.
- To summarize ongoing clinical trials and discuss the clinical application of immunotherapy for TNBC.
Main Methods:
- Review of preclinical studies investigating immunotherapy targets and mechanisms in TNBC.
- Analysis of data from early-phase clinical trials evaluating immune-checkpoint blockade and other immunotherapies in TNBC patients.
- Synthesis of information from ongoing clinical trials and expert clinical perspectives.
Main Results:
- TNBC is characterized by a higher degree of immune infiltrate compared to other breast cancer subtypes.
- Tumor-infiltrating lymphocytes (TILs) in TNBC are predictive of favorable survival and response to therapy.
- Early clinical trials indicate promising results for immunotherapy in TNBC, with ongoing studies exploring various agents and combinations.
Conclusions:
- Immunotherapy, particularly immune-checkpoint blockade, represents a promising therapeutic strategy for TNBC.
- The immunogenic nature of TNBC, evidenced by higher TILs, supports its potential for successful immunotherapy treatment.
- Further clinical investigation and exploration of immunotherapy are crucial for improving outcomes in TNBC.
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