Investigating and critically appraising the expression and potential role of androgen receptor in breast carcinoma

2011 ◽  
Vol 7 (1) ◽  
Author(s):  
Mark B. Peter ◽  
Abeer M. Shaaban ◽  
Sree Sundara Rajan ◽  
Loaie Maraqa ◽  
Kieran Horgan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Potential Role ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Continuous Variable ◽  
Endocrine Treatment ◽  
Breast Cancer Death

AbstractThe potential role of the androgen receptor (AR) as a predictive or prognostic factor in breast cancer remains unclear. We aimed to determine the prognostic significance of AR in a cohort of breast carcinomas with long-term follow-up and to critically appraise this in the context of existing literature. Four hundred and eight cases of invasive breast cancer were incorporated into tissue microarrays (TMAs). All received tamoxifen and comprised 108 cases which relapsed and 300 cases which did not. Mean follow-up time for the former was 84 months (range 1–142, SD 38.8) and for the latter was 77 months (range 11–229, SD 49.7). TMAs were immunohistochemically stained with AR and scored as a continuous variable and using the Allred score. AR expression was significantly associated with grade, recurrence on tamoxifen, non-breast cancer death estrogen receptor alpha (ERα) and progesterone receptor (PR). AR correlated significantly with better overall survival (OS) and disease-free survival (DFS) using an Allred cut-off of 4 (log rank=0.0053 and 0.0044, respectively), and 20% positive tumor cells (log rank=0.0027 and 0.0059, respectively). AR expression was additionally associated with a reduced risk of recurrence following endocrine therapy. In summary, AR positive breast tumors have better OS and DFS and are less likely to recur following endocrine treatment.

scholarly journals Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1952
Author(s):  
Elżbieta Zarychta ◽  
Barbara Ruszkowska-Ciastek ◽  
Kornel Bielawski ◽  
Piotr Rhone
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Stromal Cell ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Roc Curve Analysis ◽  
Stromal Cell Derived Factor ◽  
A Prospective Study

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

scholarly journals TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2365 ◽  
Author(s):  
Ewan Millar ◽  
Lois Browne ◽  
Iveta Slapetova ◽  
Fei Shang ◽  
Yuqi Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Automated Image Analysis ◽  
Breast Cancer Patients ◽  
Long Term Follow Up ◽  
Inflammatory Chemokines

Aim: To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Methods: Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20, CD68, Fox P3, PD-1 and PD-L1 in a clinical trial of local excision and radiotherapy randomised to a cavity boost or not (n = 485, median follow-up 16 years). Kaplan–Meier and Cox multivariate analysis (MVA) methodology were used to ascertain relationships with local recurrence (LR), overall survival (OS) and disease-free survival (DFS). NanoString BC360 gene expression panel was applied to a subset of luminal patients to identify pathways associated with LR. Results: LR was predicted by low CD8 in MVA in the whole cohort (HR 2.34, CI 1.4–4.02, p = 0.002) and luminal tumours (HR 2.19, CI 1.23–3.92, p = 0.008) with associations with increased stromal components, decreased Tregs (FoxP3), inflammatory chemokines and SOX2. Poor OS was associated with low CD20 in the whole cohort (HR 1.73, CI 1.2–2.4, p = 0.002) and luminal tumours on MVA and low PD-L1 in triple-negative cancer (HR 3.44, CI 1.5–7, p = 0.003). Conclusions: Immunophenotype adds further prognostic data to help further stratify risk of LR and OS even in TILs low-luminal tumours.

scholarly journals PD-L1 in Breast Cancers and its Prognostic Significance

2021 ◽  
Vol 11 (01) ◽  
pp. 40-43
Author(s):  
Sayher Kazmi ◽  
Sumayyah Shawana ◽  
Nighat Jamal
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumour Cells ◽  
Breast Cancers ◽  
Free Survival ◽  
Disease Free ◽  
Treat Breast Cancer ◽  
Common Malignancy

Breast cancer is the most common malignancy in females globally. Various factors are responsible for its development which include both genetic and hormonal causes. An important discovery is the role of the PD-1/PD-L1 axis in the development of cancers. The PD-1-/PD-L1 pathway plays a part in allowing tumour cells escape from the hosts immune response and hence permits the proliferation of tumour cells. PD-L1 expression has been observed in various breast cancers at distinct levels such as in tissues and in blood. Different methods have been utilized for its detection including immunohistochemistry, RNA sequencing and ELISA, amongst others. The results have been conflicting regarding the expression of PD-L1 and the prognosis of breast cancer based on parameters such as overall survival and disease free survival. Different immunotherapies have also emerged as a new modality to treat breast cancer. This review intends to explore the prognostic significance of PD-L1 expression in breast cancers.

scholarly journals The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Glutamine Metabolism ◽  
Gene Copy ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

scholarly journals Prognostic and Clinicopathological Significance of MiR-155 in Breast Cancer: A Systematic Review

2020 ◽  
Vol 21 (16) ◽  
pp. 5834
Author(s):  
Anna Maria Grimaldi ◽  
Silvia Nuzzo ◽  
Gerolama Condorelli ◽  
Marco Salvatore ◽  
Mariarosaria Incoronato
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Prognostic Biomarker ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Unmet Need ◽  
Non Invasive ◽  
Clinicopathological Significance ◽  
Present Systematic Review

There is an unmet need for novel non-invasive prognostic molecular tumour markers for breast cancer (BC). Accumulating evidence shows that miR-155 plays a pivotal role in tumorigenesis. Generally, miR-155 is considered an oncogenic miRNA promoting tumour growth, angiogenesis and aggressiveness of BC. Therefore, many researchers have focused on its use as a prognostic biomarker and therapeutic target. However, its prognostic value for BC patients remains controversial. To address this issue, the present systematic review aims to summarize the available evidence and give a picture of a prognostic significance of miR-155 in BC pathology. All eligible studies were searched on PubMed and EMBASE databases through various search strategies. Starting from 289 potential eligible records, data were examined from 28 studies, comparing tissue and circulating miR-155 expression levels with clinicopathological features and survival rates in BC patients. We discuss the pitfalls and challenges that need to be assessed to understand the power of miR-155 to respond to real clinical needs, highlighting the consistency, robustness or lack of results obtained to sate in translating this molecule to clinical practice. Our paper suggests that the prognostic role of miR-155 in the management of BC needs to be further verified.

scholarly journals A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Michael Dagher ◽  
Vance G Fowler ◽  
Patty W Wright ◽  
Milner B Staub
Keyword(s):  
Staphylococcus Aureus ◽  
Hospital Readmission ◽  
Potential Role ◽  
Review Article ◽  
Narrative Review ◽  
Oral Antibiotics ◽  
Staphylococcus Aureus Bacteremia ◽  
Complete Treatment

Abstract Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated Staphylococcus aureus bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest. This narrative review article aims to summarize key arguments for and against the use of oral antibiotics to complete treatment of uncomplicated SAB and evaluates the available evidence for specific oral regimens. We conclude that evidence suggests that oral step-down therapy can be an alternative for select patients who meet the criteria for uncomplicated SAB and will comply with medical treatment and outpatient follow-up. Of the currently studied regimens discussed in this article, linezolid has the most support, followed by fluoroquinolone plus rifampin.

scholarly journals Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
Author(s):  
Aiyu Zhu ◽  
Yan Li ◽  
Wei Song ◽  
Yumei Xu ◽  
Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

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