scholarly journals MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000937
Author(s):  
Annalisa Petrelli ◽  
Sara Erika Bellomo ◽  
Ivana Sarotto ◽  
Franziska Kubatzki ◽  
Paola Sgandurra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Endocrine Therapy ◽  
Molecular Subtype ◽  
Molecular Taxonomy ◽  
Endocrine Resistance ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Luminal Breast Cancer ◽  
Luminal A

PurposeOverexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.MethodsmiR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype.ResultsBaseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype.ConclusionsOur findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.

FOXA1 expression in Iraqi women with ER+ breast cancer: A case control study

2020 ◽  
Vol 2 (02) ◽  
Author(s):  
Iman Al-Bedairy ◽  
Mais Shamsa ◽  
Safaa aldeen Salim ◽  
Mohammed Mahdi ◽  
Karam Dawood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Molecular Subtype ◽  
Estrogen Receptor Α ◽  
Luminal Breast Cancer ◽  
Molecular Characteristics ◽  
Luminal A ◽  
Fresh Tissue ◽  
Iraqi Women ◽  
Foxa1 Expression

Background: Breast cancer is a heterogeneous disease that can be classified into many subtypes according to histopathological and molecular characteristics. Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor (α-ER)-chromatin binding and function. FOXA1 expression is related to luminal breast cancer with a good prognosis. Objectives: The present study is sought to determine the gene expression of FOXA1 in Iraqi women with ER+ breast cancer from fresh tissue. Methods: Forty-eight fresh malignant breast tissues analyzed by immunohistochemistry assay to choose ER+ sample submitted to RT-qPCR to evaluate FOXA1 gene expression. Results: ER-positive was 72.91% of the total samples, luminal A was the most common molecular subtype with 56.25%. Conclusions: Highly significant FOXA1 gene expression in Iraqi women with breast cancer makes it eligible to be a good predictor or a biomarker for breast cancer.

scholarly journals Molecular and clinical characterization of CCT2 expression at transcriptional level via 2994 samples of breast cancer

2020 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Xiangyu Wang ◽  
Xiangyi Kong ◽  
Yi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Transcriptional Level ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Worse Prognosis

Abstract BackgroundMolecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperonen CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2), a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC).MethodThrough the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology (GO) and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer.ResultsWe found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype.ConclusionIn summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

scholarly journals Luminal Versus Non-luminal Breast Cancer CDH1 Immunohistochemical Expression

2019 ◽  
Vol 70 (2) ◽  
pp. 465-469 ◽  
Author(s):  
Dana Carmen Zaha ◽  
Claudia Maria Jurca ◽  
Simona Bungau ◽  
Gabriela Cioca ◽  
Amorin Popa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Molecular Subtype ◽  
Histological Grade ◽  
Prognostic Index ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Immunohistochemical Expression ◽  
Luminal A ◽  
E Cadherin

We investigated the immunohistochemical expression of E-cadherin (product of CDH1 gene) and its correlation with clinical-pathological parameters and survival rate in the molecular groups of breast cancer. Our study included female breast cancer patients diagnosed at the Municipal Emergency Clinical Hospital Timisoara followed up five years since diagnosis using formalin fixed paraffin embedded tissue. The traditional prognostic factors (age, tumor size, histological type, histological grade, anatomical status of the lymph nodes) were abstracted from histopathology reports and we set prognostic index (the Nothingham and lymph-node prognosis index). Molecular classification on selected cases was performed in agreement with data from the literature: luminal A, B, HER2+, triple-negative. We noted positive (membranar) expressions in 43 cases (70.49 %). Negative immunoreactions for E-cadherin have been observed in all cases of lobular carcinomas (4 cases), as well as 6 cases of mixed carcinomas. A significant correlation was found between E-cadherin expression and hormonal status, tumor size, histologic type, tumor grade and molecular subtype. Most of the luminal A and B tumors were E-cadherin positive, while more than half of non-luminal tumors were E-cadherin negative. Survival rates are different in the negative and positive E-cadherin tumor groups respectively and between luminal and non-luminal groups. E-cadherin expression may be a useful prognostic marker for classifying other subgroups of breast cancer.

scholarly journals Molecular and Clinical Characterization of CCT2 Expression and Prognosis via Large-Scale Transcriptome Profile of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Wenxiang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Molecular Chaperone ◽  
Large Scale ◽  
Molecular Taxonomy ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Worse Prognosis

Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

scholarly journals Association of body mass and systemic immune-inflammation indices with endocrine therapy resistance in luminal breast cancers

2019 ◽  
Vol 47 (5) ◽  
pp. 1936-1947 ◽  
Author(s):  
Qing-xia Li ◽  
Dong-jian Shi ◽  
Li-xia Zhang ◽  
Dong-miao Wang ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Disease Free Survival ◽  
Therapy Resistance ◽  
Luminal Breast Cancer ◽  
Endocrine Therapy Resistance ◽  
Free Survival ◽  
Resistance Rates ◽  
High Bmi

Objective To explore correlations between body mass index (BMI), preoperative systemic immune-inflammation index (SII) and endocrine therapy resistance, and evaluate BMI and SII as predictors of resistance, in patients with luminal breast cancer. Methods This retrospective study included patients with luminal breast cancer who underwent endocrine therapy at Hebei General Hospital. Relationships between BMI and SII subgroups, and clinicopathological parameters were analysed using χ2-tests. Disease-free survival was assessed using Log-rank statistics. Multivariate analysis of factors related to disease progression were analysed using Cox proportional hazards model. Results Out of 161 patients, those with normal BMI and low SII had significantly lower endocrine resistance rates versus those with high BMI and SII, and BMI was significantly positively correlated with SII. High BMI or SII was associated with significantly lower disease-free survival rates. Hazard ratios for disease progression risk were 6.036, 3.508 and 1.733, for SII, BMI and TNM stage, respectively. Conclusion In patients with luminal breast cancer, high BMI (>23 kg/m2) and SII (>518 × 109/L) levels may predict high endocrine resistance rates. BMI, SII and TNM stage were independent prognostic factors for endocrine therapy resistance.

scholarly journals Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Junjeong Choi ◽  
Eun-Sol Kim ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Pentose Phosphate Pathway ◽  
Molecular Subtype ◽  
Pentose Phosphate ◽  
The Cancer Genome Atlas ◽  
Related Factor ◽  
Mrna Levels ◽  
Luminal A ◽  
Her 2 ◽  
Related Proteins

Purpose. The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. Methods. Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers. mRNA levels of these markers in publicly available data from the Cancer Genome Atlas project and Kaplan-Meier plotters were analyzed. Results. Expression of G6PDH and 6PGL was higher in HER-2 type (p<0.001 and p=0.009, resp.) and lower in luminal A type. 6PGDH expression was detected only in TNBC subtype (p<0.001). G6PDH positivity was associated with ER negativity (p=0.001), PR negativity (p=0.001), and HER-2 positivity (p<0.001), whereas 6PGL positivity was associated with higher T stage (p=0.004). The 562 expression profile from the TCGA database revealed increased expression of G6PDH and 6PG in the tumor compared with normal adjacent breast tissue. The expression of G6PDH was highest in HER-2 type. HER-2 and basal-like subtypes showed higher expression of 6PGDH than luminal types. Conclusion. PPP-related proteins are differentially expressed in breast cancer according to molecular subtype, and higher expression of G6PDH and 6PGL was noted in HER-2 subtype.

scholarly journals MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sanne Løkkegaard ◽  
Daniel Elias ◽  
Carla L. Alves ◽  
Martin V. Bennetzen ◽  
Anne-Vibeke Lænkholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Predictive Marker ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Minichromosome Maintenance ◽  
Primary Tumors

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

scholarly journals Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Luminal Breast Cancer ◽  
Luminal A ◽  
Luminal B ◽  
Lymphocyte Ratio ◽  
Cell Counts ◽  
Pre Treatment

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

scholarly journals The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1160
Author(s):  
Giusi La Camera ◽  
Luca Gelsomino ◽  
Amanda Caruso ◽  
Salvatore Panza ◽  
Ines Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Endocrine Resistance ◽  
Disease Recurrence ◽  
Estrogen Receptor Α ◽  
Research Area ◽  
Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

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