scholarly journals Therapeutic Targets In Breast Cancer Signaling: A Review

2021 ◽  
pp. 82-99
Author(s):  
Emmanuel Ifeanyi Obeagu ◽  
Quratulain Babar ◽  
C. C. N. Vincent ◽  
Chikwendu Lawrence Udenze ◽  
Richard Eze ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Predictive Biomarkers ◽  
Molecular Therapy ◽  
Therapeutic Interventions ◽  
Breast Cancers ◽  
Dominant Type ◽  
Cellular Pathways ◽  
Breast Tissues ◽  
Human Epidermal Receptor

For women, the most dominant type of cancer is breast cancer and perhaps one of the most recognizedreasons of death. This is a disorder of many distinct traits, many of which are known as positive hormone receptor, human epidermal receptor-2 (HER2+), and three negative breast cancers (TNBC). Drugs that directly target and kill tumors constitute a rapidly-growing form of molecular therapy for cancer patients. Analysis reveals that stable breast tissue cells exhibit receptors which aren't usually present. As a result, it is imperative to cognize the molecular roots of breast cancer and the myriad compromised pathology-related processes and pathways to ensure progresses in early diagnosis and prevention. This study demonstrates essential cellular pathways relevant for breast cancer including improvements in cell proliferation, apoptosis, and hormone balances in breast tissues. On the basis of these notions, we consider how breast cancer is associated to the creation of potentially therapeutic interventions and predictive biomarkers.

scholarly journals Immunotherapy in Triple-Negative Breast Cancer: Present and Future

2019 ◽  
Vol 11 (4) ◽  
pp. 259-271 ◽  
Author(s):  
Isaac Kim ◽  
Katherine Sanchez ◽  
Heather L. McArthur ◽  
David Page
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Survival Benefit ◽  
Triple Negative ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Phase Iii ◽  
Breast Cancers ◽  
Effective Treatment Option

Abstract Purpose of Review Immunotherapy is emerging as an effective treatment option for metastatic triple-negative breast cancer. In this review, we summarize clinical data of immunotherapy in triple-negative breast cancer and comment on future directions in the field. Recent Findings IMpassion130 was a phase III trial that demonstrated progression-free survival benefit, and potentially overall survival benefit, of first-line chemotherapy (nab-paclitaxel) plus anti-programmed death ligand 1 (PD-L1) atezolizumab, among PD-L1-positive metastatic triple-negative breast cancers. Studies are ongoing to evaluate other combination therapies with immune checkpoint blockade in TNBC, and to evaluate efficacy in PD-L1-negative tumors and in later lines of therapy. Summary Immunotherapy is now a standard option in the treatment of triple-negative breast cancer. Ongoing trials may expand the degree of clinical benefit. Further work is ongoing to identify novel predictive biomarkers, which in the future may enable a personalized approach of combination immunotherapy.

scholarly journals Survival outcomes are associated with genomic instability in luminal breast cancers

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245042
Author(s):  
Lydia King ◽  
Andrew Flaus ◽  
Emma Holian ◽  
Aaron Golden
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Cancer Survival ◽  
Molecular Taxonomy ◽  
Gene Signature ◽  
Therapeutic Interventions ◽  
Survival Outcomes ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A

Breast cancer is the leading cause of cancer related death among women. Breast cancers are generally diagnosed and treated based on clinical and histopathological features, along with subtype classification determined by the Prosigna Breast Cancer Prognostic Gene Signature Assay (also known as PAM50). Currently the copy number alteration (CNA) landscape of the tumour is not considered. We set out to examine the role of genomic instability (GI) in breast cancer survival since CNAs reflect GI and correlate with survival in other cancers. We focused on the 70% of breast cancers classified as luminal and carried out a comprehensive survival and association analysis using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to determine whether CNA Score Quartiles derived from absolute CNA counts are associated with survival. Analysis revealed that patients diagnosed with luminal A breast cancer have a CNA landscape associated with disease specific survival, suggesting that CNA Score can provide a statistically robust prognostic factor. Furthermore, stratification of patients into subtypes based on gene expression has shown that luminal A and B cases overlap, and it is in this region we largely observe luminal A cases with reduced survival outlook. Therefore, luminal A breast cancer patients with quantitatively elevated CNA counts may benefit from more aggressive therapy. This demonstrates how individual genomic landscapes can facilitate personalisation of therapeutic interventions to optimise survival outcomes.

scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Estrogen Receptor Α ◽  
Epidemiological Studies ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Increased Risk ◽  
The Impact

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

scholarly journals Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pauliina M. Munne ◽  
Lahja Martikainen ◽  
Iiris Räty ◽  
Kia Bertula ◽  
Nonappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Therapeutic Interventions ◽  
Preclinical Model ◽  
Matrix Stiffness ◽  
Breast Cancers ◽  
Ex Vivo Model ◽  
Major Barrier ◽  
The Matrix

AbstractBreast cancer is now globally the most frequent cancer and leading cause of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

scholarly journals Pathophysiological roles of ERα in the ER signaling mediated oncogenesis of breast cancer

2021 ◽  
Vol 18 (4) ◽  
pp. 289-302
Author(s):  
Sultan Abda Neja ◽  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Breast Tissue ◽  
Transcriptional Activity ◽  
Review Literature ◽  
Bibliographic Databases ◽  
Target Cells ◽  
Breast Cancers ◽  
Oncogenic Pathways ◽  
Estradiol 17Β

Introduction. Estrogen receptors (ER) are members of nuclear receptors that act in the ER signaling pathway regulating the pathophysiology of hormone-responsive target cells including breast tissue. Aim. This detailled review literature was written on the pathophysiology of ER signaling as well as the effect altered ERα and associated pathway derangement in the oncogenesis of breast cancer. Material and methods. This review was performed according to systematic literature search of three major bibliographic databases (Scopus, PubMed, and Cochran). Analysis of the literature. In this pathway, estrogen receptor alpha (ERα) is a key estradiol-17β (E2) induced transcription factor that has been implicated in the initiation and development of the major fraction of breast cancers. Hence understanding the ERα-mediated ER signaling that results in alterations from normal phenotypic features of breast tissue to the oncogenic features of breast cancer is important. The oncogenic effect of ERα in ER signaling is driven by combinations of molecular assets within the cancer cells. Normally, the transcriptional activity of ERα is controlled by tight regulation of its protein level inside the cells. Altered stability and activity of ERα due to its phosphorylation, ubiquitination, glycosylation, sumoylation, and acetylation events can trigger oncogenic ER signaling. Conclusion. The function and activity of ERα is also modulated by its interaction with coregulators as well as crosstalk with oncogenic factors from other oncogenic pathways. These all events increase the complexity of the progression of ER+ breast cancer and its response to endocrine therapy.

An Intelligent-Based Wavelet Classifier for Accurate Prediction of Breast Cancer

2018 ◽  
pp. 306-319 ◽  
Author(s):  
Anandakumar Haldorai ◽  
Arulmurugan Ramu
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Roc Curve ◽  
Breast Tissue ◽  
Wavelet Neural Network ◽  
Clinical Database ◽  
New Approach ◽  
X Ray ◽  
Breast Tissues

The detection of cancer in the breast is done using mammograms (x-ray images). The authors propose a CAD framework for distinguishing little changes in mammogram which may demonstrate malignancies which are too little to be felt either by the lady herself or by a radiologist. In this chapter, they build up a framework for analysis, visualization, and prediction of cancer in breast tissue by utilizing Intelligent based wavelet classifier. Intelligent-based wavelet classifier is a new approach constructed using texture value and wavelet neural network. The proposed framework is applied to the genuine clinical database of 160 mammograms gathered from mammogram screening focuses. The execution of the CAD framework is examined utilizing ROC curve. This will help the specialists in determination of the breast tissues either cancerous or noncancerous in an accurate way.

scholarly journals Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S39384 ◽  
Author(s):  
David N. Danforth
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
High Risk ◽  
Breast Tissue ◽  
Sporadic Breast Cancer ◽  
Normal Breast Tissue ◽  
Normal Breast ◽  
Breast Carcinogenesis ◽  
Molecular Changes ◽  
Breast Tissues

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women.

Raman Spectroscopic Characterization of Human Breast Tissues: Implications for Breast Cancer Diagnosis

1993 ◽  
Vol 47 (6) ◽  
pp. 787-791 ◽  
Author(s):  
Douglas C. B. Redd ◽  
Zhe Chuan Feng ◽  
Kwok To Yue ◽  
Ted S. Gansler
Keyword(s):  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Breast Tissue ◽  
Breast Cancer Diagnosis ◽  
Spectroscopic Characterization ◽  
Small Contribution ◽  
Breast Cancers ◽  
Normal Tissues ◽  
Benign Breast Tissue ◽  
Breast Tissues

Development and application of laser-based diagnostic and therapeutic procedures have been hindered by the current technical inadequacies in tissue diagnosis and characterization. It is now possible to apply the techniques of Raman spectroscopy to achieve rapid, noninvasive, and nondestructive differentiation of diseased from normal tissues. Normal and diseased breast tissues were examined by Raman spectroscopy. The Raman spectra obtained contain features that are attributable to various amounts of carotenoids and lipids. A small contribution from a heme-type signal was detected in some samples of clinically abnormal yet histopathologically benign breast tissue, while a much stronger heme-type signal was detected in most of the breast cancers. Raman spectra of diseased breast tissue (benign and malignant) also show markedly diminished to absent contributions from lipids and reduced contributions from carotenoids. This laser-based spectroscopic modality is readily adaptable to reflected light microscopy and optical fiber techniques, making it potentially useful as an aid in real-time diagnosis, and may thus find application in the fields of histopathology and interventional radiology.

Are dietary factors involved in the association of CDH4 methylation and breast cancer risk?

2021 ◽  
pp. 1-36
Author(s):  
Nannan Zhang ◽  
Liangliang Li ◽  
Zhiping Long ◽  
Jinghang Du ◽  
Shuo Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Tissue ◽  
Dietary Habits ◽  
Peripheral Blood Leukocyte ◽  
Dietary Factors ◽  
Interactive Effects ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Specific Pcr

Abstract DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits have been shown to alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell-cell adhesion glycoproteins. We conducted a case-control study (380 newly-diagnosed breast cancers and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL), as well as its combined and interactive effects with dietary factors and lifestyle on BC risk. A case-only study (335 newly-diagnosed breast cancers) was conducted to analyze the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation were detected using quantitative methylation specific PCR (qMSP). Unconditional logistic regressions were used to analyze the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj)= 2.70, 95% confidence interval (CI)= 1.90-3.83, P<0.001). CDH4 hypermethylation also showed significant combined effects with the consumption of <500 g/week vegetables (ORadj=4.33, 95% CI=2.63-7.10), ≤3 times/week allium vegetables (ORadj=7.00, 95% CI=4.17-11.77), <3 times/week fish (ORadj=7.92, 95% CI=3.79-16.53), <3 times/week milk (ORadj=6.30, 95% CI=3.41-11.66), >3 times/week overnight food (ORadj=4.63, 95% CI=2.69-7.99), ≥250 g/week pork (ORadj=5.59, 95% CI=2.94-10.62), and <1 time/month physical activity (ORadj=4.72, 95% CI=2.87-7.76). Moreover, consuming milk ≥ 1 times/month was significantly related with decreased risk of CDH4 methylation (OR=0.61, 95% CI=0.38-0.99) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

scholarly journals Epigenetic Dysregulation of KCNK9 Imprinting and Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6031
Author(s):  
David A. Skaar ◽  
Eric C. Dietze ◽  
Jackelyn A. Alva-Ornelas ◽  
David Ann ◽  
Dustin E. Schones ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Membrane Potential ◽  
High Risk ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Breast Tissue ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Breast Cancers ◽  
High Risk Women

Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, KCNK9 gene amplification accounts for increased expression in <10% of these breast cancers. Here, we showed that KCNK9 is imprinted in breast tissue and identified a differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of KCNK9, occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans (p = 0.006), but not in Caucasians (p = 0.70). KCNK9 hypomethylation was also found in non-cancerous tissue from 77% of women at high-risk of developing breast cancer. Functional studies demonstrated that the KCNK9 gene product, TASK3, regulates mitochondrial membrane potential and apoptosis-sensitivity. In TNBC cells and non-cancerous mammary epithelial cells from high-risk women, hypomethylation of the KCNK9 DMR predicts for increased TASK3 expression and mitochondrial membrane potential (p < 0.001). This is the first identification of the KCNK9 DMR in mammary epithelial cells and demonstration that its hypomethylation in breast cancer is associated with increases in both mitochondrial membrane potential and apoptosis resistance. The high frequency of hypomethylation of the KCNK9 DMR in TNBC and non-cancerous breast tissue from high-risk women provides evidence that hypomethylation of the KNCK9 DMR/TASK3 overexpression may serve as a marker of risk and a target for prevention of TNBC, particularly in African American women.

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