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Published on: May 2, 2025
Targeting the host immune system: PD-1 and PD-L1 antibodies and breast cancer
Shaheenah Dawood1, Hope S Rugo
1aDepartment of Medical Oncology, Dubai Hospital, UAE bUniversity of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Purpose Of Review:
This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer.
Recent Findings:
Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease. Variability in requirements for tumor PD-L1 expression, and variations in testing complicate cross trial comparisons. A fifth phase Ib trial reported a 38% response rate in metastatic triple negative breast cancer treated with the combination of a PD-L1 inhibitor and nab-paclitaxel chemotherapy. Treatment is generally well tolerated, with low rates of immune toxicity including hypothyroidism, pneumonitis, hepatitis, colitis, and hypophysitis, occurring even months after the end of therapy.
Summary:
Immune checkpoint inhibitor therapy has recently been shown to have clinical efficacy in the treatment of breast cancer. The most compelling data are in the triple negative subtype, with responses documented in hormone receptor positive disease as well. Numerous trials are evaluating various combination strategies and biomarkers in early and late stage disease to enhance immunogenicity and response.
Insights
Immune checkpoint inhibitors targeting PD-1 and PD-L1 show efficacy in breast cancer, particularly triple-negative subtypes. Combination therapies may enhance response rates in metastatic disease.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Immune checkpoint inhibitor therapy demonstrates clinical efficacy in breast cancer treatment.
- The PD-1 axis plays a crucial role in regulating anti-tumor immunity.
- Triple-negative breast cancer shows promising responses to PD-1/PD-L1 inhibition.
Purpose of the Study:
- To review the role of the PD-1 axis in breast cancer.
- To summarize current data on PD-1 and PD-L1 inhibitors in breast cancer.
- To discuss future directions for PD-1/PD-L1 inhibition in breast cancer therapy.
Main Methods:
- Review of Phase I and Ib clinical trials involving PD-1 and PD-L1 inhibitors in metastatic breast cancer.
- Analysis of response rates in different breast cancer subtypes (triple-negative vs. hormone receptor-positive).
- Evaluation of combination strategies, including with nab-paclitaxel chemotherapy.
Main Results:
- Monotherapy PD-1/PD-L1 inhibitors yielded durable responses (4.8-19%) in metastatic breast cancer.
- Higher response rates observed in triple-negative breast cancer compared to hormone receptor-positive disease.
- A combination trial reported a 38% response rate in metastatic triple-negative breast cancer with a PD-L1 inhibitor and nab-paclitaxel.
Conclusions:
- PD-1/PD-L1 inhibitors are a promising therapeutic strategy for breast cancer, especially triple-negative subtype.
- Combination strategies and biomarker research are ongoing to enhance immunogenicity and response.
- Treatment is generally well-tolerated with low rates of immune-related adverse events.
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