scholarly journals Expression of Programmed Cell Death-1 (PD-1) and Its Ligand (PD-L1) in Breast Cancers and Its Association with Clinicopathological Parameters: A Study from North India

2021 ◽  
Author(s):  
Anoushika Mehan ◽  
Michael Leonard Anthony ◽  
Pranoy Paul ◽  
Anjum Syed ◽  
Nilotpal Chowdhury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
North India ◽  
Clinicopathological Parameters ◽  
Ki 67 ◽  
Programmed Cell Death 1 ◽  
Percent Positivity

Abstract Introduction Cancer immunotherapy targeting the programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) axis has revolutionized cancer therapy. PD-L1 also serves as a predictive marker for such therapy. To assess the potential of such therapy in any cancer, the positivity of PD-1 and PD-L1 in such cancers needs to be assessed. However, such studies for breast cancer are lacking in South Asia. We aimed to estimate the positivity of PD-L1 and PD-1 receptors in breast cancer and its various clinicopathological groups in our patient population. Materials and Methods We studied the immunoexpression of PD-1 and PD-L1 in 103 histologically proven invasive carcinoma breast cases from October 2018 to April 2019. The percent positivity of PD-1 and PD-L1 with 95% confidence intervals (CI) was estimated for all the cases as well as groups defined by stage, grade, molecular subtype, hormone receptor status, Ki-67, and age. Results PD-1 positivity was seen in 72 (69.9%) cases (95% CI: 60.1–78.6). PD-L1 immunoexpression was seen in 61 (59.2%) cases (95% CI: 49.1–68.8) in immune cells and in 39 (37.9%) cases (95% CI: 28.5–50.0) in tumor cells. No significant association was found between PD-1, PD-L1 and age, overall clinical stage, grade, size, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Moderate-to-high PD-1 and PD-L1 immunopositivity was seen in all subtypes of breast cancer. Conclusion PD-1 and PD-L1 is expressed in all subgroups of breast carcinoma. Patients in all such groups are amenable to immunotherapy, provided they are found suitable otherwise.

scholarly journals Study of Gene Expression of Programmed Cell Death Ligand 1 (PD-L1) in Breast Cancer Patients

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 2-2
Author(s):  
H Gadelrab ◽  
M Mokhtar ◽  
H Morsy ◽  
M Elnaggar
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Patients ◽  
Therapeutic Response ◽  
Female Breast Cancer ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Female Breast

Introduction: Breast cancer is the most frequently occurring cancer among females and the second most common cancer overall. Programmed Cell Death Ligand 1 (PD-L1) plays an important role in blocking ‘cancer-immunity cycle’ and is considered as a major inhibitory pathway. The aim of the present study was to clarify the alterations of expression of PD-L1 in peripheral blood mononuclear cytes (PBMCs) of female breast cancer patients and analyze its association with clinico-pathological criteria as well as therapeutic response. Materials and Methods: The study was conducted on 45 female breast cancer patients and 45 female controls. Blood samples were collected followed by PBMCs isolation, total RNA extraction, reverse transcription and finally, quantitative polymerase chain reaction (qPCR) using SYBR Green DNA binding dye. Expression levels of PD-L1 were calculated and then compared with clinicopathological parameters of the patients in addition to initial therapeutic response. Results: A significant difference was detected for PD-L1 expression levels in breast cancer patients compared to controls. A significant association with age, metastatic breast cancer, estrogen receptor (ER) negative status as well as high concentrations of cancer antigen 15-3 (CA15-3) was detected. On the other hand, no significant association was recognized with tumor size, lymph nodal status, histopathological type, grade, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER-2) status, triple negative, among de novo and recurrent metastatic patients and for the number of metastatic sites as well as the therapeutic response. Conclusions: This study paves the way of the use of PD-L1 as a noninvasive prognostic and diagnostic biomarker for poor prognosis of breast cancer.

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 Future prospects for breast cancer immunotherapy

2018 ◽  
pp. 12-16
Author(s):  
V. F. Semiglazov ◽  
A. I. Tseluiko ◽  
R. V. Donskikh ◽  
P. V. Krivorotko ◽  
G. A. Dashyan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Surgical Treatment ◽  
Programmed Cell Death ◽  
T Lymphocyte ◽  
Standard Treatment ◽  
Immune Checkpoints ◽  
Future Prospects ◽  
Programmed Cell Death 1

Immunotherapy has already become an important component of the standard treatment of patients with advanced cancer. Most treatment methods include monoclonal antibodies (mAbs) that block immune checkpoints, in particular, the programmed cell death 1 (PD-1) receptor and its ligand 1 (PD-L1) or are directed against T-lymphocyte-associated protein 4 (CTLA-4). The future prospects for immuno-oncology will be to determine whether these agents can be more effective if administered in a postoperative adjuvant or in a neoadjuvant regimen prior to surgical treatment. Vaccine therapy has shown promising results, and this therapy is especially attractive due to absence of pronounced toxicity.

scholarly journals Pathogenic variants inBRCA1/2genes among patientswith triple-negative breast cancer: a case series

Mastology ◽  
2021 ◽  
Vol 31 ◽  
Author(s):  
Rafael Everton Assunção Ribeiro da Costa ◽  
Fergus Tomás Rocha de Oliveira ◽  
Ana Lúcia Nascimento Araújo ◽  
Sabas Carlos Vieira
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Case Series ◽  
Neoplastic Disease ◽  
Ki 67 ◽  
Pathogenic Variants

Triple-negative breast cancer (TNBC) is an uncommon molecular subtype (representing 15%–20% of breast cancers) characterized by the non-expression of estrogen receptor, progesterone receptor, and human epidermal growth receptor factor 2. More aggressive and lethal, TNBC is often associated with pathogenic variants in BRCA1/2 genes. This study aimed to describe a series of seven cases of patients with TNBC and pathogenic variants in BRCA1/2 genes. All patients were female and under 50 years of age at diagnosis. Four of them presented a family history of breast cancer and/or other neoplasms. The predominant clinical stage was IIB, and the main anatomopathological stage was pT2pN0M0. The mean tumor size in the series was 2.5 cm (1.0 to 3.2 cm). Ki-67 was > 30% in all patients. Three cases (43%) had pathological complete response, and only one presented extensive residual disease after neoadjuvant chemotherapy. Six patients showed pathogenic variants in BRCA1 (86%) and one in BRCA2+ (14%). After a mean follow-up of 38 months (19 to 68 months), five patients were alive and without neoplastic disease, and two progressed to metastasis.

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.

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.

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