scholarly journals Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I–III patients treated with standard therapy

2020 ◽  
Vol 136 ◽  
pp. 7-15 ◽  
Author(s):  
Maria Vittoria Dieci ◽  
Vassilena Tsvetkova ◽  
Gaia Griguolo ◽  
Federica Miglietta ◽  
Giulia Tasca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Standard Therapy ◽  
Triple Negative ◽  
Stage I ◽  
Prognostic Models ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals The Association of Tumor-Infiltrating Lymphocytes and Programmed Cell Death 1 Expression with the Incidence of Distant Metastasis in Triple-Negative Breast Cancer Subjects in Sanglah General Hospital, Bali, Indonesia

2021 ◽  
pp. 347-351
Author(s):  
I Wayan Sudarsa ◽  
I Putu Ari Gunawan ◽  
Ida Bagus Tjakra Wibawa Manuaba
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
General Hospital ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Programmed Cell Death 1 ◽  
Infiltrating Lymphocytes

The triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a high rate of distant metastasis. The tumor immunity microenvironment plays an important role, including tumor-infiltrating lymphocytes (TIL) and PD-1 (programmed cell death 1)/PD-L1 (programmed cell death-ligand 1), in promoting TNBC aggressiveness. This study aimed to determine the association of TIL and PD-L1 expression with the incidence of distant metastasis in TNBC. This study is a cross-sectional study involving TNBC subjects at Sanglah General Hospital, Denpasar, conducted in 2019. The parameters analyzed were the expression of TIL, PD-L1, and the incidence of distant metastasis. The expression of TIL was analyzed histopathologically while PD-L1 was measured with Ventana PD-L1 kit test. Subject characteristics were obtained from medical records. Data were collected and analyzed by SPSS 22.0. As many as 31 subjects with TNBC were included in this study, with 51.6% subjects with distant metastasis. The majority of subjects with distant metastasis had low TIL and low tumoral PD-L1 but high PD-L1 stromal in TIL. From statistical analysis, only PD-L1 stromal in TIL expression was associated significantly with distant metastasis (p = 0.043). In conclusion, there was a significant association between PD-L1 stromal in TIL and the incidence of distant metastasis in TNBC.

scholarly journals Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting

2016 ◽  
Vol 10s1 ◽  
pp. CMO.S34540 ◽  
Author(s):  
Paula García-Teijido ◽  
María Luque Cabal ◽  
Ignacio Peláez Fernández ◽  
Yolanda Fernández Pérez
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Infiltrating Lymphocytes ◽  
Cell Death Protein

Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials.

Prognostic value of stromal tumour infiltrating lymphocytes and programmed cell death-ligand 1 expression in breast cancer

2017 ◽  
Vol 70 (10) ◽  
pp. 860-867 ◽  
Author(s):  
António Polónia ◽  
Regina Pinto ◽  
Jorge F Cameselle-Teijeiro ◽  
Fernando C Schmitt ◽  
Joana Paredes
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Prognostic Value ◽  
Stromal Tumour ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Radiotherapy with the anti-programmed cell death ligand-1 immune checkpoint blocker avelumab: acute toxicities in triple-negative breast cancer

2018 ◽  
Vol 36 (1) ◽  
Author(s):  
Eliana La Rocca ◽  
Michela Dispinzieri ◽  
Laura Lozza ◽  
Gabriella Mariani ◽  
Serena Di Cosimo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative

scholarly journals Efficacy and safety profiles of programmed cell death-1/programmed cell death ligand-1 inhibitors in the treatment of triple-negative breast cancer: A comprehensive systematic review

2019 ◽  
Vol 13 (2) ◽  
Author(s):  
Gilbert Lazarus ◽  
Jessica Audrey ◽  
Anthony William Brian Iskandar
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Programmed Cell Death 1 ◽  
Grade 3

Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) showed great potentials in treating malignancies and may serve as potential therapies for TNBC. This systematic review aims to evaluate the efficacy and safety profiles of PD-1/PD-L1 inhibitors in the treatment of TNBC. Literature search was performed via PubMed, EBSCOhost, Scopus, and CENTRAL databases, selecting studies which evaluated the use of anti-PD-1/PDL1 for TNBC from inception until February 2019. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). Overall, 7 studies evaluating outcomes of 1395 patients with TNBC were included in this systematic review. Anti-PD-1/PD-L1 showed significant antitumor effect, proven by their promising response (objective response rate (ORR), 18.5-39.4%) and survival rates (median overall survival (OS), 9.2-21.3 months). Moreover, anti- PD-1/PD-L1 yielded better outcomes when given as first-line therapy, and overexpression of PD-L1 in tumors showed better therapeutic effects. On the other hands, safety profiles were similar across agents and generally acceptable, with grade ≥3 treatment- related adverse effects (AEs) ranging from 9.5% to 15.6% and no new AEs were experienced by TNBC patients. Most grade ≥3 AEs are immune-mediated, which are manifested as neutropenia, fatigue, peripheral neuropathy, and anemia. PD-1/PD-L1 inhibitors showed promising efficacy and tolerable AEs, and thus may benefit TNBC patients. Further studies of randomized controlled trials with larger populations are needed to better confirm the potential of these agents.

scholarly journals Mismatch Repair Deficiency and Microsatellite Instability in Triple-Negative Breast Cancer: A Retrospective Study of 440 Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin-yu Ren ◽  
Yu Song ◽  
Jing Wang ◽  
Long-yun Chen ◽  
Jun-yi Pang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Low Frequency ◽  
Clinicopathological Parameters ◽  
Tissue Samples

PurposeTo investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.MethodsWe retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.ResultsThe median age of the cohort was 49 years (range: 24–90 years) with a median follow-up period of 68 months (range: 1–170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible EPCAM deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.ConclusionsThe incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.

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