HER2 overexpression and correlation with other significant clinicopathologic parameters in Ivorian breast cancer women

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.

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The Relationship Between eNOS Polymorphisms With Age, Smoking, Body Mass Index, and Clinicopathologic Parameters in Patients With Breast Cancer in Comparison With a Control Group

Clinical Breast Cancer ◽

10.1016/j.clbc.2019.12.013 ◽

2020 ◽

Vol 20 (3) ◽

pp. e344-e352

Author(s):

Zahra Tahmasebi Fard

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Body Mass ◽

Control Group ◽

Clinicopathologic Parameters ◽

The Relationship ◽

Enos Polymorphisms

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Nanolipoprotein mediated Her2 protein transfection induces malignant transformation in human breast acinar cultures

10.1101/2020.08.25.265512 ◽

2020 ◽

Author(s):

Wei He ◽

Angela C. Evans ◽

Matthew Coleman ◽

Claire Robertson

Keyword(s):

Breast Cancer ◽

Malignant Transformation ◽

Cell Surface Receptor ◽

Cell Phenotype ◽

Her2 Overexpression ◽

Malignant Cells ◽

Transformation Techniques ◽

Her2 Protein ◽

Surface Receptor ◽

Protein Transfection

AbstractHer2 overexpression is associated with an aggressive form of breast cancer and malignant transformation. We sought to determine if a nano-carrier system could introduce Her2 protein to non-malignant cells and determine the effects on cell phenotype and transcriptome. With stimulation with Her2-NLPs, we observed uptake of Her2 protein and a decreased probability of individual non-malignant cells forming polar growth arrested acinar-like structures. The NLP delivery system alone or Her2-NLPs plus trastuzumab showed no effect on acinar organization rate. Transcriptomics revealed essentially no effect of empty NLPs versus untreated cells whereas Her2-NLPs versus either untreated or empty NLP treated cells revealed upregulation of several factors associated with breast cancer. Pathway analysis also suggested that known nodes downstream of Her2 were activated in response to Her2-NLP treatment. This suggests that Her2-NLPs are sufficient for malignant transformation of non-malignant cells and that this system offers a new model for studying cell surface receptor signaling without genomic modification or transformation techniques.

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Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

International Journal of Cancer Research and Molecular Mechanisms ◽

10.16966/2381-3318.148 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Duman BB ◽

Cil T

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Maintenance Therapy ◽

Hormone Receptor ◽

Tumor Heterogeneity ◽

Hormone Receptors ◽

Triple Negative ◽

Neoadjuvant Treatment ◽

Metastatic Breast ◽

Her2 Overexpression

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

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Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers13164139 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4139

Author(s):

Pere Llinàs-Arias ◽

Sandra Íñiguez-Muñoz ◽

Kelly McCann ◽

Leonie Voorwerk ◽

Javier I. J. Orozco ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Immune Escape ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Regulatory Elements ◽

Her2 Overexpression ◽

Breast Cancers ◽

Cancer Subtypes

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression. This malignancy, representing 15–20% of breast cancers, is a clinical challenge due to the lack of targeted treatments, higher intrinsic aggressiveness, and worse outcomes than other breast cancer subtypes. Immune checkpoint inhibitors have shown promising efficacy for early-stage and advanced TNBC, but this seems limited to a subgroup of patients. Understanding the underlying mechanisms that determine immunotherapy efficiency is essential to identifying which TNBC patients will respond to immunotherapy-based treatments and help to develop new therapeutic strategies. Emerging evidence supports that epigenetic alterations, including aberrant chromatin architecture conformation and the modulation of gene regulatory elements, are critical mechanisms for immune escape. These alterations are particularly interesting since they can be reverted through the inhibition of epigenetic regulators. For that reason, several recent studies suggest that the combination of epigenetic drugs and immunotherapeutic agents can boost anticancer immune responses. In this review, we focused on the contribution of epigenetics to the crosstalk between immune and cancer cells, its relevance on immunotherapy response in TNBC, and the potential benefits of combined treatments.

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Outcome of breast cancer patients regarding obesity and complications: Analysis of risk factors

Romanian Medical Journal ◽

10.37897/rmj.2021.1.14 ◽

2021 ◽

Vol 68 (1) ◽

pp. 77-86

Author(s):

Iuliana Pantelimon ◽

◽

Laurentia Nicoleta Gales ◽

Maria Daniela Tanasescu ◽

Irina Nita ◽

...

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Prognostic Factors ◽

Disease Progression ◽

Body Mass ◽

Type Ii Diabetes ◽

The Body ◽

Proliferation Index ◽

Her2 Overexpression ◽

Type Ii

Introduction. Breast cancer is the leading cause of cancer death in Romania. In the context in which the treatments available for this pathology have increased curability, the identification of negative prognostic factors involved in the evolution of this disease seems essential to improve the overall survival as well as the time to disease progression. Aim. The aim of this study is to identify the role of prognostic factors such as ki67 proliferation index, the presence of tumour estrogen receptors, HER2 overexpression, the presence of secondary determinations at diagnosis, the association of obesity and type II diabetes. Methods. 50 patients diagnosed with breast cancer treated in the Elias University Emergency Hospital Bucharest were retrospectively followed, for which the progression was documented at the time of elaboration of this study. Thus, a database was developed in which data were entered on age, body mass index, immunohistochemical characteristics of breast tumours, the presence/absence of metastases at diagnosis and the association of type II diabetes. Statistical calculations were performed to highlight a possible correlation between obesity (quantified by measuring body mass index) and tumour aggressiveness (quantified by ki67 proliferation index) as well as statistical evaluation of potential prognostic factors that would influence time, until the disease progresses. Results. Within this group, no correlation could be established between the presence of an increased body mass index and the value of the ki67 proliferation index (p = 0.38). The mean value of the body mass index for this group of unselected patients was 28.76 ± 4.81 (DS) most patients are therefore overweight or obese. The factors involved in the evolution of breast cancer that influenced the early progression of the disease were: the proliferation index ki67 (p <0.05), the presence of metastases at diagnosis (p < 0.0001) and the association of type II diabetes (p = 0.0085). The value of the body mass index did not influence the time to disease progression according to statistical calculations in this group probably due to the small number of normal weight patients included (p = 0.34).

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Aberrant ALOX5 Activation Correlates with HER2 Status and Mediates Breast Cancer Biological Activities through Multiple Mechanisms

BioMed Research International ◽

10.1155/2020/1703531 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Xiao Zhou ◽

Yi Jiang ◽

Qiuyun Li ◽

Zhen Huang ◽

Huawei Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Biological Activities ◽

Critical Role ◽

Her2 Overexpression ◽

Her2 Positive ◽

Mesenchymal Transition ◽

And Migration ◽

Expression And Activity

Arachidonate lipoxygenases (ALOX) have been implicated in playing a critical role in tumorigenesis, development, and metastasis. We previously reported that ALOX12 is involved in breast cancer chemoresistance. In this study, we demonstrate that the ALOX5 activation correlates with the HER2 expression and mediates breast cancer growth and migration. We found that the ALOX5 expression and activity were upregulated in breast cancer patients, particularly in those tissues with HER2-positive. ALOX5 upregulation was also observed in HER2-positive breast cancer cells. In contrast, HER2 inhibition led to decreased expression and activity of ALOX5 but not ALOX5AP, suggesting that HER2 specifically regulates the ALOX5 expression and activity in breast cancer cells. We further demonstrated that ALOX5 is important for breast cancer biological activities with the predominant roles in growth and migration, likely through RhoA, focal adhesion, and PI3K/Akt/mTOR signaling but not epithelial mesenchymal transition (EMT). Our work is the first to report a correlation between the ALOX5 activity and HER2 overexpression in breast cancer. Our findings also highlight the therapeutic value of inhibiting ALOX5 in breast cancer, particularly those patients with the HER2 overexpression.

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Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue

BioMed Research International ◽

10.1155/2017/2321916 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Gedmante Radziuviene ◽

Allan Rasmusson ◽

Renaldas Augulis ◽

Daiva Lesciute-Krilaviciene ◽

Aida Laurinaviciene ◽

...

Keyword(s):

Breast Cancer ◽

Image Analysis ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

High Capacity ◽

Automated Image Analysis ◽

Cancer Tissue ◽

Her2 Overexpression ◽

Borderline Cases

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions.

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