Immune Checkpoint Inhibition for Triple-negative Breast Cancer

2016 ◽  
Vol 12 (01) ◽  
pp. 31 ◽  
Author(s):  
Poornima Saha ◽  
Rita Nanda ◽  
◽  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Multiple Tumor ◽  
Clinical Challenge ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Tumor Types

Triple-negative breast cancer remains an important clinical challenge with no targeted therapy available for treatment. Recently, drugs targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) axis have been investigated, with promising responses across multiple tumor types. Two drugs—pembrolizumab and atezolizumab—have recently been explored in advanced triple-negative breast cancer and have demonstrated promising responses.

scholarly journals Current Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3529
Author(s):  
Karan Mediratta ◽  
Sara El-Sahli ◽  
Vanessa D’Costa ◽  
Lisheng Wang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Promising Candidate ◽  
The Past ◽  
Programmed Death ◽  
Programmed Death 1

With improved understanding of the immunogenicity of triple-negative breast cancer (TNBC), immunotherapy has emerged as a promising candidate to treat this lethal disease owing to the lack of specific targets and effective treatments. While immune checkpoint inhibition (ICI) has been effectively used in immunotherapy for several types of solid tumor, monotherapies targeting programmed death 1 (PD-1), its ligand PD-L1, or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have shown little efficacy for TNBC patients. Over the past few years, various therapeutic candidates have been reviewed, attempting to improve ICI efficacy on TNBC through combinatorial treatment. In this review, we describe the clinical limitations of ICI and illustrate candidates from an immunological, pharmacological, and metabolic perspective that may potentiate therapy to improve the outcomes of TNBC patients.

scholarly journals 7 Analytical comparison of a PD-L1 22C3 antibody laboratory-developed test protocol on the Benchmark XT and PD-L1 IHC 22C3 pharmDx: pan-tumor and triple-negative breast cancer samples

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A7-A7
Author(s):  
Gilad Vainer ◽  
Ghadeer Zatara ◽  
Lingkang Huang ◽  
Shanthy Nuti ◽  
Shanthy Nuti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Intraclass Correlation ◽  
Continuous Variable ◽  
Small Sample ◽  
List Type ◽  
Test Protocol ◽  
Multiple Tumor ◽  
Tumor Types

BackgroundPD-L1 IHC 22C3 pharmDx is an FDA-approved companion diagnostic for pembrolizumab across multiple tumor types designed for use on the Autostainer Link 48 (AL48). Many pathology laboratories do not have access to the AL48 and therefore do not use PD-L1 IHC 22C3 pharmDx but instead assess PD-L1 using laboratory-developed tests (LDTs) on the Ventana BenchMark platform. We compared our PD-L1 22C3 antibody-based LDT on the BenchMark XT platform with PD-L1 IHC 22C3 pharmDx using cervical cancer (CC), head and neck squamous cell carcinoma (HNSCC), urothelial carcinoma (UC), esophageal SCC (ESCC), and triple-negative breast cancer (TNBC) samples.MethodsTumor specimens from patients with CC, HNSCC, UC, ESCC, and TNBC were stained with the 22C3 antibody, scored using the LDT on the BenchMark XT as previously described,1 and compared with PD-L1 IHC 22C3 pharmDx scored by a trained pathologist, who measured PD-L1 with the use of combined positive score (CPS) and standard cutoffs (HNSCC and CC, ≥1; UC, ESCC, and TNBC, ≥10). Agreement in PD-L1 CPS as determined using the LDT and the PD-L1 IHC 22C3 pharmDx was evaluated.Results423 samples with CC (n = 77), HNSCC (n = 126), UC (n = 121), ESCC (n = 80), and TNBC (n = 19) were evaluated in this study. The pan-tumor (CC, HNSCC, UC, and ESCC) intraclass correlation coefficient (ICC) of PD-L1 CPS as a continuous variable was 0.95 (95% CI, 0.94%–0.96%); Spearman correlations were 0.95. ICC (95% CI) was 0.92 (0.88–0.95) for CC, 0.97 (0.96–0.98) for HNSCC, 0.95 (0.92–0.97) for UC, and 0.92 (0.88–0.95) for ESCC; Spearman correlation was 0.93, 0.96, 0.92, and 0.89, respectively. The overall percentage agreement at the respective CPS cutoff was 96% (CC), 96% (HNSCC), 96% (UC), and 90% (ESCC). Staining patterns by 22C3 LDT and PD-L1 IHC 22C3 pharmDx were also very similar in our TNBC pilot study; however, correlation was not calculated because of the small sample numbers.ConclusionsThe PD-L1 22C3 antibody-based LDT on the BenchMark XT demonstrated high concordance with PD-L1 IHC 22C3 pharmDx. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody across several tumor types. Further validation for TNBC is ongoing to confirm the data from the pilot run.ReferenceNeuman T, et al. J Thorac Oncol. 2016;11:1863–1868.

Abstract 1484: SCD-1 blockade sensitizes triple negative breast cancer to immune checkpoint inhibition

2021 ◽  
Author(s):  
Sneha Vivekanandhan ◽  
Justyna Trynda ◽  
Laura A. Marlow ◽  
Barath shreeder ◽  
James L. Miller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

scholarly journals Immune Checkpoint Inhibition for Triple-Negative Breast Cancer: Current Landscape and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Huimei Yi ◽  
Ying Li ◽  
Yuan Tan ◽  
Shujun Fu ◽  
Faqing Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Early Stage ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Durable Response

Triple-negative breast cancer (TNBC) is characterized by the lack of clinically significant levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Owing to the aggressive nature and the emergence of resistance to chemotherapeutic drugs, patients with TNBC have a worse prognosis than other subtypes of breast cancer. Currently, immunotherapy using checkpoint blockade has been shown to produce unprecedented rates of long-lasting responses in patients with a variety of cancers. Although breast tumors, in general, are not highly immunogenic, TNBC has a higher level of lymphocyte infiltration, suggesting that TNBC patients may be more responsive to immunotherapy. The identification/characterization of immune checkpoint molecules, i.e., programmed cell death protein 1 (PD1), programmed cell death ligand 1 (PDL1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), represents a major advancement in the field of cancer immunotherapy. These molecules function to suppress signals downstream of T cell receptor (TCR) activation, leading to elimination of cytotoxic T lymphocytes (CTLs) and suppression of anti-tumor immunity. For TNBC, which has not seen substantial advances in clinical management for decades, immune checkpoint inhibition offers the opportunity of durable response and potential long-term benefit. In clinical investigations, immune checkpoint inhibition has yielded promising results in patients with early-stage as well as advanced TNBC. This review summarizes the recent development of immune checkpoint inhibition in TNBC, focusing on humanized antibodies targeting the PD1/PDL1 and the CTLA4 pathways.

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