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Updated: Nov 9, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Current treatment landscape and emerging therapies for metastatic triple-negative breast cancer
1Touro College of Pharmacy, New York, NY.
Abstract:
A lack of therapeutically targetable molecular alterations and its aggressive nature make triple-negative breast cancer (TNBC) a challenging disease. Chemotherapy is standard of care for most patients with metastatic disease, but median overall survival is less than 18 months. Unravelling the molecular underpinnings of TNBC revealed it to be a potentially highly immunogenic subtype within a more broadly immunologically inert cancer type, suggesting that it may respond to immunotherapy. An urgent need for new therapies is being filled in part by recent successes with immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor 1 and programmed death ligand 1 (PD-L1). Although single-agent ICIs had limited activity, exploration of rational combinations has yielded 2 new FDA approvals for atezolizumab and pembrolizumab in combination with chemotherapy, leading to a new standard of care for patients with PD-L1-positive disease. Two FDA-approved companion diagnostic PD-L1 assays are available to identify patients eligible for immunotherapy treatment, but other biomarkers of response are also being examined. Ongoing clinical trials are also evaluating a range of targeted therapies as combination partners, which may have immunomodulatory effects in addition to their main mechanism of action, complementing the activity of ICIs. This article will evaluate the current and emerging clinical trends in the use of ICIs as part of combination regimens in the treatment of patients with metastatic TNBC.
Insights
Triple-negative breast cancer (TNBC) is aggressive, but immunotherapy offers new hope. Immune checkpoint inhibitors (ICIs) combined with chemotherapy are now a standard of care for PD-L1 positive metastatic TNBC.
Area of Science:
- Oncology
- Immunology
- Medical Science
Background:
- Triple-negative breast cancer (TNBC) presents therapeutic challenges due to its aggressive nature and lack of targetable alterations.
- Current chemotherapy offers limited survival benefits for metastatic TNBC patients, with median overall survival under 18 months.
Purpose of the Study:
- To review current and emerging clinical trends in using immune checkpoint inhibitors (ICIs) in combination regimens for metastatic TNBC.
- To highlight the evolving role of immunotherapy in treating this challenging breast cancer subtype.
Main Methods:
- Review of recent clinical trial data and FDA approvals for immunotherapy in TNBC.
- Examination of biomarkers, including PD-L1 expression, for predicting response to ICIs.
- Analysis of combination strategies involving ICIs and chemotherapy or targeted therapies.
Main Results:
- Single-agent ICIs showed limited efficacy, but combinations with chemotherapy have led to new FDA approvals for PD-L1 positive metastatic TNBC.
- Atezolizumab and pembrolizumab in combination with chemotherapy represent a new standard of care for eligible patients.
- Ongoing trials explore targeted therapies with potential immunomodulatory effects as combination partners for ICIs.
Conclusions:
- Immune checkpoint inhibitors, particularly in combination regimens, are transforming the treatment landscape for metastatic TNBC.
- PD-L1 expression is a key biomarker, but research into additional response predictors is ongoing.
- Combination therapies hold promise for improving outcomes in TNBC by synergizing ICI activity with other treatment modalities.
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