The efficacy and safety of PD-1/PD-L1 inhibitors in breast cancer: a systematic review and meta-analysis

Xiao, Bo-Ya; Lin, Guo-He; Zhao, Yuliang; Wang, Bi-Cheng

doi:10.21037/tcr-19-3020

Cited by 8 publications

(4 citation statements)

References 46 publications

(31 reference statements)

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“…To date, the US Food and Drug Administration has approved several monoclonal antibodies that function by blocking immune checkpoint activity. These include the anti- CTLA -4 antibody ipilimumab, anti- PD1 antibodies pembrolizumab, (FDA approved drug for high-risk, early-stage TNBC ), nivolumab, cemiplimab, and the anti- PD-L1 antibodies atezolizumab (first FDA-approved immunotherapy drug for locally advanced or metastatic TNBC ), avelumab, and durvalumab [ 137 ].…”

Section: Current Immunotherapeutic Strategies Of Tnbcmentioning

confidence: 99%

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Kudelova

Smolár

Holubeková

et al. 2022

IJMS

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Heterogeneity of triple-negative breast cancer is well known at clinical, histopathological, and molecular levels. Genomic instability and greater mutation rates, which may result in the creation of neoantigens and enhanced immunogenicity, are additional characteristics of this breast cancer type. Clinical outcome is poor due to early age of onset, high metastatic potential, and increased likelihood of distant recurrence. Consequently, efforts to elucidate molecular mechanisms of breast cancer development, progression, and metastatic spread have been initiated to improve treatment options and improve outcomes for these patients. The extremely complex and heterogeneous tumor immune microenvironment is made up of several cell types and commonly possesses disorganized gene expression. Altered signaling pathways are mainly associated with mutated genes including p53, PIK3CA, and MAPK, and which are positively correlated with genes regulating immune response. Of note, particular immunity-associated genes could be used in prognostic indexes to assess the most effective management. Recent findings highlight the fact that long non-coding RNAs also play an important role in shaping tumor microenvironment formation, and can mediate tumor immune evasion. Identification of molecular signatures, through the use of multi-omics approaches, and effector pathways that drive early stages of the carcinogenic process are important steps in developing new strategies for targeted cancer treatment and prevention. Advances in immunotherapy by remodeling the host immune system to eradicate tumor cells have great promise to lead to novel therapeutic strategies. Current research is focused on combining immune checkpoint inhibition with chemotherapy, PARP inhibitors, cancer vaccines, or natural killer cell therapy. Targeted therapies may improve therapeutic response, eliminate therapeutic resistance, and improve overall patient survival. In the future, these evolving advancements should be implemented for personalized medicine and state-of-art management of cancer patients.

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Section: Current Immunotherapeutic Strategies Of Tnbcmentioning

confidence: 99%

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Kudelova

Smolár

Holubeková

et al. 2022

IJMS

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“…Immune checkpoint inhibitors play an important role in the treatment of cancers (20) and anti-PD-1/PD-L1 treatments are widely used in advanced or metastatic cancers (21)(22)(23). However, the use of PD-1/PD-L1 inhibitors in the adjuvant setting for patients with cancer is still a tentative approach.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer

Liang

Chen

et al. 2022

Exp Ther Med

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Anti-program med cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) antibodies have been widely used in cancers. The present study aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in human cancers. Studies were searched from Cochrane Library, PubMed and Embase databases. Randomized controlled trials (RCTs) that investigated adjuvant therapy with anti-PD-1/PD-L1 agents in solid cancers were eligible for inclusion. As the primary focus of the meta-analysis, clinical outcome measures including overall survival (OS), disease-free survival (DFS), and adverse events (AEs) were analyzed by Stata 15.0 software. A total of six RCTs (n=4,436) met the inclusion criteria. The DFS [hazard ratio (HR)=0.71; 95% confidence interval (CI): 0.63-0.78; P<0.001] and OS (HR=0.66, 95% CI: 0.46-0.86, P<0.001) of patients were significantly prolonged by adjuvant immunotherapy. Subgroup analysis indicated that significantly improved DFS was observed in patients treated with different anti-PD-1/PD-L1 drugs (nivolumab, pembrolizumab, or atezolizumab), as well as in those with different tumors (melanoma, urothelial carcinoma, esophageal or gastroesophageal junction cancer, or renal cell carcinoma), and PD-L1 status [negative (<1%) or positive (≥1%)]. However, PD-1/PD-L1 inhibitors was associated with increased ≥ grade 3 treatment-related AEs (odds ratio=1.63; 95% CI: 1.20-2.21; P=0.002). The available evidence suggests that adjuvant therapy with PD-1/PD-L1 inhibitors provided more survival benefit than placebo for patients with cancer, with increased grade 3 or higher AEs. Prospero registration no. CRD42021290654.

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“…This interaction results in a greater T lymphocyte-mounted immune response to cancerous cells characterized by elevated CD4+ and CD8+ T cells in circulation and in the tumor microenvironment [75]. Recent preclinical studies and clinical trials support the use of anti-programmed cell death protein 1/programmed death ligand 1 pathway (anti-PD-1/PDL-1) therapy in some individuals with metastatic or triple negative breast cancer, which are difficult to treat [76,77]. Not all breast cancers are PD-1+, but therapies to disrupt this system has been reported as well tolerated for those individuals and it is being investigated as a potential adjuvant to conventional breast cancer therapies [76].…”

Section: Immunotherapymentioning

confidence: 99%

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Sampsell

Hao²,

Reimer

2020

IJMS

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Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.

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The efficacy and safety of PD-1/PD-L1 inhibitors in breast cancer: a systematic review and meta-analysis

Cited by 8 publications

References 46 publications

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

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