PD-1/PD-L1 Pathway in Breast Cancer

Schütz, Florian; S, Stefanovic; Mayer, Luisa; Au, Alexandra von; Domschke, Christoph; Sohn, Christof

doi:10.1159/000464353

Cited by 131 publications

(94 citation statements)

References 42 publications

(32 reference statements)

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“…Once engaged, the PD1/PD‐L1 pathway leads to the mitigation of T‐cell‐mediated immune response through the inhibition of T‐cell activation and the promotion of the regulatory function of T lymphocytes. In solid tumors, this process may be exploited by the tumor microenvironment to silence or at least attenuate the antitumor immune response .…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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Section: Introductionmentioning

confidence: 99%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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“…In breast cancer, immunotherapy is being explored, in particular in patients with tumors expressing PD-L1 and infiltrated with lymphocytes [266] . Potential response to PD-1 or PD-L1 inhibitors was demonstrated in metastatic TNBC [267] and HER2 + breast cancers [268] . However, because the number of potential neoantigens available for immune response in most breast cancers, responses are modest compared with other cancers such as lung and melanoma, the use of check-point inhibitors may require combination with other therapies [269] .…”

Section: Check Point Inhibitorsmentioning

confidence: 99%

Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

Peyvandi¹,

Lan²,

Lorusso³

et al. 2019

JCMT

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Breast cancer remains the main cause of cancer-related mortality for women worldwide. Main cause of death is the development of therapy-resistant metastases. Relapses occur with a bimodal temporal distribution, with a first peak at 1-2 years after initial therapy and a second peak 2-3 years later. This discontinuous growth kinetics is consistent with the notion that disseminated cancer cells can remain dormant over a prolonged period of time before resuming growth. How cancer cells enter, sustain and exit dormancy, are unanswered questions with relevance to cancer biology, monitoring and therapy. Investigating mechanisms of breast cancer dormancy remains challenging, as in patients the condition is elusive and experimentally there are only a few models that recapitulate the clinical condition. Thus, developing new models to identify clinically relevant mechanisms and candidate therapeutic targets may open new avenues for novel therapies to induce and prolong dormancy. We have observed that cells surviving chemotherapy can enter a state of immunological dormancy. Using this model, we identified IRF-7/Interferon type I/IFNRA as signaling axis essential for this effect. Here we will review concepts and recent developments in cancer metastasis and dormancy with emphasis on breast cancer, and elaborate strategies to exploit them therapeutically.

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“…Anti-PD-1/PD-L1 therapy is a novel immune-checkpoint inhibition therapy and anti-PD-1/PD-L1 agents, such as nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab have been widely applied to treat various types of cancer (128-130). Anti-PD-1/PD-L1 agents have shown antitumor activity in BC, especially in the triple-negative subtypes of breast cancer (TNBC) (131,132). But PD-L1 expression is associated with HER2 + status and there is an independent poor prognostic impact of PD-L1 in HER2 + BCs (132)(133)(134).…”

Section: Pd-1 and Pd-l1 Agents Programmed Death Ligand 1 (Pd-l1)mentioning

confidence: 99%

“…Anti-PD-1/PD-L1 agents have shown antitumor activity in BC, especially in the triple-negative subtypes of breast cancer (TNBC) (131,132). But PD-L1 expression is associated with HER2 + status and there is an independent poor prognostic impact of PD-L1 in HER2 + BCs (132)(133)(134). In a phase 1b trial which 168 patients with MBC received avelumab, avelumab showed an acceptable clinical activity (135).…”

Section: Pd-1 and Pd-l1 Agents Programmed Death Ligand 1 (Pd-l1)mentioning

confidence: 99%

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

et al. 2018

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Abstract.Human epidermal growth factor receptor-2 positive breast cancer (HER2 + BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2 + BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2 + BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2 + BC patients in the future.

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PD-1/PD-L1 Pathway in Breast Cancer

Cited by 131 publications

References 42 publications

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

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