Strategic Aspects of NPY-Based Monoclonal Antibodies for Diagnosis and Treatment of Breast Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 1097-1102
Author(s):  
Drashti Desai ◽  
Pravin Shende
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Diagnosis And Treatment ◽  
Detection Methods ◽  
Active Immunotherapy ◽  
Immune Checkpoints ◽  
Proliferation Index ◽  
Protein Fusion ◽  
Ki 67 ◽  
Cost Efficient

: Immunotherapy emerges as a treatment strategy for breast cancer marker, diagnosis and treatment. In this review, monoclonal antibodies (mAbs)-based passive and peptide vaccines as active immunotherapy approaches like activation of B-cells and T-cells are studied. Passive immunotherapy is mAbs-based therapy effective against tumor cells, which acts by targeting HER2, IGF 1R, VEGF, BCSC and immune checkpoints. Neuropeptide Y (NPY) and GPCR are the areas of interest to target BC metastases for on-targeting therapeutic action. Neuropeptide S (NPS) or NPS receptor 1, acts as a biomarker for Neuroendocrine tumors (NET), mostly characterized by synaptophysin and chromogranin-A expression or Ki-67 proliferation index. The protein fusion technologies arise as a promising avenue in plant expression systems for increased recombinant Ab accumulation and cost-efficient purification. Recently, mAbs-based immunotherapy effectiveness is appreciated as a novel therapeutic combination of chemotherapy and immunotherapy to reduce the side effects and improve therapeutic responsiveness. Synthetic drug resistance will be overcome by mAbs-based therapy through several clinical trials and detection methods need to be optimized for accuracy and precision. Pharmacokinetic attributes need to be accessed for preferred receptor-agonist activity without ligand accumulation.

Neuroendocrine differentiation in metastatic breast cancer following CDK 4/6 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13029-e13029
Author(s):  
Sakina Sekkate ◽  
Laure Ladrat ◽  
Christelle Pouliquen ◽  
Celine Callens ◽  
Jean Francois Geay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Aromatase Inhibitor ◽  
Neuroendocrine Differentiation ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Proliferation Index ◽  
Castration Resistant Prostate Cancer ◽  
Metastatic Tumors ◽  
Ki 67

e13029 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered as a standard of care based on the compelling data across all landmark trials. Methods: We report our experience about two cases with metastatic breast cancer treated by CDK4/6 inhibitor in combination with an aromatase inhibitor, which develop neuroendocrine differentiation. After observing an unusual massive progression, a biopsy of the metastasis was performed in both patients. Both histological analysis confirmed a lobular breast cancer with small cell neuroendocrine features and a high proliferation index (KI 67 90%). An NGS (Next generation sequencing) profile was realized on primary and metastatic tumors to detect new acquired genomic alterations. Results: The comparative analysis of the NGS results of primary and metastatic tumors revealed the occurrence of several events in both patients under treatment. For one patient, we identified new mutations in the genes CDH1, FANCG, PIK3CA, PTEN and TP53, which did not exist initially. For the second patient, we found an amplification of the segment containing FGFR1, CCND1, FGF4, FGF3, FADD genes and the deletion of the segment containing RB1 andTP53 genes. Such events were not observed on the primary tumor. Conclusions: Prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer but neuroendocrine differentiation is atypical in breast carcinoma. In case of unusual rapidly progressive disease after CDK4/6 inhibitor, biopsy of new metastases should be recommanded to search neuroendocrine differentiation, or druggable mutations to guide the treatment.

Relationship of Ki-67 proliferative index and metastatic tumor of breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22190-e22190
Author(s):  
Kokoro Kobayashi ◽  
Yoshinori Ito ◽  
Akiko Ogiya ◽  
Naoya Gomi ◽  
Rie Horii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Tumor ◽  
Labeling Index ◽  
Proliferation Index ◽  
Luminal Breast Cancer ◽  
Line Treatment ◽  
Metastatic Tumors ◽  
Ki 67 ◽  
Primary Tumors

e22190 Background: The metastatic breast tumor tends to be more aggressive with high proliferation, but this has not been proven in clinical sampling of metastatic tumors. Methods: Forty-eight patients who had histological specimens of both primary and metastatic sites of luminal breast cancer (ER and/or PgR positive and HER2 negative) were examined. We classified them as luminal A (LA) with Ki-67 labeling index of less than 14% and as luminal B (LB) with Ki-67 labeling index of more than 14%. We analyzed their overall survival (OS) and progression free survival (PFS) of 1st line treatment of each subtype of primary and metastatic tumors. Results: Subtypes of primary tumors and metastatic tumors were as follows; the primary tumor: LA; 34 patients (70.8%), LB; 14 (29.2%), metastatic tumors: LA; 21 (43.8%), LB; 27 (56.2%). Patients with LA of the primary tumor demonstrated statistically longer OS (LA; 72.5 months, LB 39.6 months, p=0.009). OS depended on the subtype of the primary tumor. In contrast, patients with LB of a metastatic tumor showed a statistically worse PFS (LA; 20.5 months, LB; 11.5 months, p=0.040). PFS of the 1st line treatment for MBC depended on the subtype of the metastatic tumor. Conclusions: The frequency of LB was increased on metastatic tumors and tended to acquire a higher proliferation index. This suggests that characterization of metastatic tumors could be better as an indicator of subsequent treatment for MBC. [Table: see text]

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 Role of MiRNAs and It’s Single Nucleotide Polymorphism in Breast Cancer

2021 ◽  
Author(s):  
Debarshi Roy ◽  
Ramesh Bandla ◽  
Praveen Boddana ◽  
Rajesh Medisetty ◽  
Raghu Gogada
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Diagnosis And Treatment ◽  
Mirna Sequence ◽  
Diagnostic Tools ◽  
Rna Sequences ◽  
Ki 67 ◽  
Single Nucleotide ◽  
Cancer Occurrence ◽  
Non Coding Rna

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

scholarly journals Monoclonal Antibodies for Immunohistochemical Diagnosis of Breast Cancer

2021 ◽  
Vol 15 (1) ◽  
pp. 157-163
Author(s):  
Aigerim Turgimbayeva ◽  
Assel Issabekova ◽  
Assylbek Zhylkibayev ◽  
Saule Eskendirova
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Molecular Genetic ◽  
Tumour Response ◽  
Progesterone Receptors ◽  
Pass Rate ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Expression Levels ◽  
Immunohistochemical Diagnosis

Breast cancer is a leading malignant disease in women worldwide, although its pathology is visually localised. Currently, it has been proven that the parameters of molecular genetic biomarkers, including oncoprotein HER2, proliferation markers Ki-67, oestrogen receptors ER, and progesterone receptors PgR, are associated with breast carcinogenesis and are a reflection of the biological aggression of the tumour. The significance of these biomarkers in signalling pathways and genetic mechanisms of carcinogenesis has been described, as well as the relationship between the expression levels of each biomarker and the tumour response to appropriate therapy. The primary antibody that imparts specificity to IHC is based on the monoclonal antibodies (mAbs) as the main immunoreagent that enables reliable identification of breast cancer cells. The most commonly used antibodies to molecular biomarkers for IHC were determined in accordance with indicators of laboratory use and efficiency (pass rate) of HER2, Ki-67, ER, PgR assessments in the NordiQC breast cancer module. The discovery of the complete structure of these biomarkers and the design of their domains and subdomains by genetic engineering methods enable the synthesis of effective monoclonal antibodies. Quantitative indicators of the expression levels of tumour biomarkers of breast cancer were determined using mAb, depending on epitope specificity and affinity.

Automated digital image analysis and manual counting of Ki-67 proliferation index in patients with breast cancer

2017 ◽  
Vol 37 (2) ◽  
pp. 228-235
Author(s):  
Mervat M.F. El-Deftar ◽  
Samir S. Amer ◽  
Eman M.O. El-Touny ◽  
Amany Aboubakr ◽  
Heba El-Zawahry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Image Analysis ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Proliferation Index ◽  
Ki 67 ◽  
Manual Counting

A retrospective study of immunohistochemical detection of Ki67 and correlation with ER, PR, and HER2-neu status in invasive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21132-e21132
Author(s):  
Deepa Meda Prakash ◽  
Swarna Shivakumar ◽  
P P Bapsy
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Tumor Size ◽  
Histological Grade ◽  
Biological Behavior ◽  
Proliferation Index ◽  
Poor Correlation ◽  
Nuclear Staining ◽  
Ki 67 ◽  
Therapeutic Decisions

e21132 Background: Carcinoma breast is a heterogeneous group of disease. Several prognostic factors are known to predict the biological behavior and clinical outcome of breast cancer, including proliferation index, tumor size, age, histological grade, hormone receptors and Her2Neu status. Of theses proliferative index is the most important parameter in predicting tumor aggressiveness and prognosis. Ki67 is a nuclear protein, tightly linked to the cell cycle and is a marker of cell proliferation. High Ki67 usually correlates with a poor prognosis in breast cancer. Methods: This exploratory study is initiated whether Ki67 will be an additional prognostic factor. Immunohistochemical staining of Ki 67 was performed on formalin fixed paraffin embedded blocks of 50 cases of histologically confirmed breast cancer. Ki 67 expression based on distinct nuclear staining of tumor cells was assessed semiquantitatively as, nil (no immunostaining), low (≤10% immunopositivity), high (>10% immunopositivity) by light microscope. ER, PR, Her 2neu status and clinico-pathological parameters were analyzed and correlated with Ki67 immunostaining using the x2 test. Results: Our study showed high Ki 67 staining in 24 cases(48%), low immunostaining in 18 cases(36%) and was nil in 5 cases (10%) and was inconclusive in 3 cases(6%) (core biopsies). There was an inverse correlation of Ki 67 with ER, PR scores in 32 cases (64%) and positive correlation was seen in 28 cases (56%) with Her2 neu status. A good correlation was also observed with mitotic index in 37cases (74%) and histological grade in 29 cases (58%). Good correlation was seen with large tumor size in 24 cases(48%) and metastatic disease 9 cases (64%). Poor correlation was observed with node positive 22 cases (44%). High Ki 67 expression with good treatment response was seen in 13 cases (26%). Conclusions: Based on our study, Ki 67 score may prove to be an important prognostic factor in breast cancer and thereby, useful in making therapeutic decisions. But this is being explored in a large prospective study.

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