scholarly journals Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 636
Author(s):  
Hsing-Ju Wu ◽  
Pei-Yi Chu
Keyword(s):  
Breast Cancer ◽  
Normal Breast ◽  
New Drugs ◽  
Cancer Type ◽  
Luminal A ◽  
Luminal B ◽  
Therapeutic Implications ◽  
Whole Cells ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER−, PR−, and HER2−), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed. In this review, we summarize and focus on the recent discoveries of promising macromolecules and cell-based biomarkers for the diagnosis and prognosis of breast cancer and provide implications for therapeutic strategies.

Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Ki67 Index ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Ki 67 ◽  
Luminal B ◽  
Therapeutic Implications ◽  
Significant Difference

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

scholarly journals Differential expression of platelet activating factor acetylhydrolase 1b in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Platelet Activating Factor ◽  
Normal Breast ◽  
Luminal A ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Luminal B ◽  
Platelet Activating Factor Acetylhydrolase

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding platelet activating factor acetylhydrolase 1b, PAFAH1B3, when comparing primary tumors of the breast to the tissue of origin, the normal breast. PAFAH1B3 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PAFAH1B3 in primary tumors of the breast was correlated with overall survival in patients with luminal A and luminal B type cancers. PAFAH1B3 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Molecular subtyping of breast cancer intrinsic taxonomy with oligonucleotide microarray and NanoString nCounter

2021 ◽  
Author(s):  
Yen-Jen Chen ◽  
Ching-Shui Huang ◽  
Nam-Nhut Phan ◽  
Tzu-Pin Lu ◽  
Chih-Yi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kappa Statistic ◽  
Normal Breast ◽  
Oligonucleotide Microarray ◽  
Breast Cancers ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Cross Platform ◽  
Breast Tissues

Breast cancer intrinsic subtypes have been identified based on the transcription of a predefined gene expression (GE) profiles and algorithm (PAM50). This study compared molecular subtyping with oligonucleotide microarray and NanoString nCounter assay. A total of 109 Taiwanese breast cancers (24 with adjacent normal breast tissues) were assayed with Affymetrix Human Genome U133 plus 2.0 microarrays and 144 were assayed with the NanoString nCounter while 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction) was performed, and 16 out of 24 (67%) matched normal breasts were categorized as the normal breast-like subtype. For 64 breast cancers assayed for both platforms, 41 (65%, one unclassified by microarray) were predicted with an identical subtype, resulting in a fair Kappa statistic of 0.60. Taking nCounter subtyping as the gold standard, prediction accuracy was 43% (3/7), 81% (13/16), 25% (5/20), and 100% (20/20) for basal-like, HER2-enriched, luminal A and luminal B subtype predicted from microarray GE profiles. Microarray identified more luminal B cases from luminal A subtype predicted by nCounter. It’s not uncommon to use microarray for breast cancer molecular subtyping for research. Our study showed that fundamental discrepancy existed between distinct GE assays, and cross platform equivalence should be carefully appraised when molecular subtyping was conducted with oligonucleotide microarray.

scholarly journals Differential expression of ANLN in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Actin Binding ◽  
Luminal A ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Luminal B

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the anillin actin binding protein, ANLN, when comparing primary tumors of the breast to the tissue of origin, the normal breast. ANLN was also differentially expressed in the tumor cells of patients with triple negative breast cancer. ANLN mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of ANLN in primary tumors of the breast was correlated with overall survival in patients with luminal A and luminal B subtype cancers. ANLN may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Subtypes of Breast Cancer in Northern India- An Immunohistomolecular Subtypes of Invasive Breast Cancer

2020 ◽  
Author(s):  
Amit Kumar Sinha ◽  
Amrita Ghosh
Keyword(s):  
Breast Cancer ◽  
Therapeutic Response ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Normal Breast ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Molecular Subclass ◽  
Epidermal Growth

Introduction: Breast cancer is a heterogeneous disease that may differ in therapeutic response and prognosis despite similarities in histopathologic types, grade and stage. Molecular studies have identified distinct subtypes of breast carcinoma each having unique recognisable phenotypes and clinical outcomes. Aim: To study the histomorphological features and Immunohistochemical (IHC) profile of breast cancer, to study the distribution of molecular subclass, and to study the morphological features of different molecular subclasses and to determine the association between the pathological features associated with adverse prognosis with the molecular subclass. Materials and Methods: Present study was a prospective cross-sectional observational study based on mastectomy specimens of 122 cases of consecutive cases of invasive breast cancer submitted from June 2012 to February 2014 in Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. On IHC staining with Estrogen Receptors (ER), Progesterone Receptors (PR), Human Epidermal growth factor Receptor 2 (HER2), Cytokeratin (CK5/6) and Epidermal Growth Factor Receptor (EGFR) these cases were classified into Luminal A, Luminal B, HER2 overexpression, basal like and normal breast like molecular subclass. All statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS, Inc., Chicago, IL, USA). Results: The proportion of each subytpes detected in present study were: Luminal A-28.69% (35), Luminal B-17.21% (21), HER2 over expressing-25.41% (31), Basal Like Breast Carcinoma (BLBC)-26.23% (32) and the rest unclassified category (normal breast like)-2.46% (3). The following variables were significantly associated with molecular breast cancer subtypes. The tumours of BLBC and HER2 overexpressing were larger, poorly differentiated, higher mitotic index, more number of positive lymph nodes and with more geographic and central necrosis than Luminal A group. These features were statistically significant (p<0.05). Conclusion: Identification of molecular subtype of breast cancer is extremely important for predicting prognosis and therapeutic response of the breast cancers and thus has role in management of patients of breast cancers. BLBC is a molecular subtype of breast cancer known for its aggressive behaviour and poor prognosis is identified by expression of basal CKs.

scholarly journals Differential expression of protein regulator of cytokinesis 1 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Luminal B

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the protein regulator of cytokinesis 1, PRC1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. PRC1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. PRC1 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PRC1 in primary tumors of the breast was correlated with overall survival in patients with basal, luminal A, and luminal B subtype cancer, but in a contrary manner. PRC1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of MMP11 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Luminal B

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the matrix metallopeptidase 11, MMP11, when comparing primary tumors of the breast to the tissue of origin, the normal breast. MMP11 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. MMP11 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of MMP11 in primary tumors of the breast was correlated with overall survival in patients with luminal A and luminal B subtype cancer, but in a contrary manner. MMP11 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Oct4 Is Not a Crucial Factor in Breast Invasive Ductal Carcinoma in Contrast to Recent Beliefs

2020 ◽  
Author(s):  
Ata Abbasi ◽  
Farahnaz Noroozinia ◽  
Sonia Hosseinzadeh ◽  
Mohammad Amin Abbasi ◽  
Samira Anvar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma ◽  
Positive Control ◽  
Normal Breast ◽  
Luminal A ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Luminal B ◽  
Oct4 Expression

We aimed to determine the frequency of Octamer binding transcription factor 4 (Oct4) expression in human invasive ductal carcinoma. 72 paraffin-embedded samples of breast cancer were enrolled. All blocks were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and Oct4 by immunohistochemistry (IHC) method. Of 72 enrolled cases, the mean age was 49.6±1.42 years. 18 (25%) of cases were luminal A, 14 (19.4%) were Her2 positive, 31 (43%) were luminal B, and 9 (12.5%) were triple-negative. IHC staining for Oct4 revealed no Oct4 expression in breast cancer samples. The staining was repeated twice, and seminoma was used as a positive control in each run. The results of both repeats were the same, and none of the examined samples showed Oct4 expression. We found no Oct4 expression in breast cancer samples examined in our study. We also did not find Oct4 expression in normal breast tissue. Our study is one of the few studies which has evaluated Oct4 expression in human breast cancer on tissue samples and is one of the least that has reported no expression of Oct4 in breast cancer.

scholarly journals Differential expression of the denticleless E3 ubiquitin protein ligase homolog in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Normal Breast ◽  
Luminal A ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Luminal B ◽  
Ubiquitin Protein Ligase

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the denticleless E3 ubiquitin protein ligase homolog, DTL, when comparing primary tumors of the breast to the tissue of origin, the normal breast. DTL mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of DTL in primary tumors of the breast was correlated with overall survival in patients with luminal A and luminal B type cancers. DTL may be of relevance to initiation, maintenance or progression of cancers of the female breast.

AGE FEATURES OF MOLECULAR-BIOLOGICAL SUBTYPES OF BREAST CANCER

2020 ◽  
Vol 17 (2) ◽  
pp. 187-192
Author(s):  
E.A. Novikova ◽  
◽  
O.V. Kostromina ◽  
D.V. Mikhailov ◽  
S.L. Leontiev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Age Groups ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Age Related ◽  
Age Features ◽  
Immunohistochemical Studies ◽  
Triple Negative Subtype

Aim. The aim of the study was to determine the presence of peculiarities of the age structure in patients with various surrogate molecular biological subtypes of breast cancer. Materials and research methods. This work analyzes the age-related characteristics of the occurrence of molecular biological subtypes in 499 patients with invasive breast cancer. All cases were divided into 5 molecular biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. The average age of the patients was 53.4±0.39 years, the predominant group was patients from 50 to 60 years (37.2% of the total). Research results. In patients under 40 years old, the triple negative subtype prevailed (44.8%). Luminal A subtype prevailed in the groups 51-60 years old (more than 41.4%) and over 60 years old (39.7%). Luminal B (Her2-) subtype was equally found in all age groups.

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