Expression of enhancer of zeste homologue 2, correlated with HIF-1α, to refine relapse risk and predict poor outcome for breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 538-538
Author(s):  
Min Dong ◽  
XinJuan Fan ◽  
Zhan-Hong Chen ◽  
Xing Li ◽  
Tian tian Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal Subtype ◽  
Prognostic Effect ◽  
Enhancer Of Zeste

538 Background: Overexpression of enhancer of zeste homologue 2 (EZH2), a key component of polycomb proteins, has been linked to aggressive tumor behavior for breast cancer. In vitro, hypoxia-inducible factor 1 alpha (HIF-1α) transcriptionally activates EZH2 and promotes breast tumor initiating cells progression. Here, we characterized the clinicopathological effect of HIF-1α and EZH2 in breast cancer patients. Methods: Tumor specimens from 410 luminal subtype breast cancer patients were used to construct tissue microarray. EZH2 and HIF-1α level were examined by immunohistochemistry staining and Western blot analysis. With the 5-year follow up, the prognostic effect of EZH2 was subjected to multivariate analysis. Results: EZH2 and HIF-1α were highly expressed in 99 (24.1%) and 272 (70.6%) patients, respectively. EZH2 overexpression was associated with high histological grade (P=0.030), lymphatic invasion (P=0.025), HER2 overexpression (P=0.005) and hypoxic condition (P<0.001). Forced expression of EZH2 predicted a poor 5-year overall survival (OS, 74.8% vs. 93.4%, P=0.001), disease-free survival (DFS, 72.2% vs. 88.6%, P=0.031), local failure-free survival (LFFS, 95.7% vs. 97.9%, P=0.045) and distant metastasis-free survival (DMFS, 75.4% vs. 90.5%, P=0.039). However, the prognostic effect of HIF-1α was not detected for breast cancer. Cox multivariate analysis confirmed that EZH2 was an independent prognostic factor for OS, DFS and LFFS. Moreover, a positive correlation was detected between EZH2 and HIF-1α (r=0.299, P<0.001). Importantly, tumors with HIF-1α and EZH2 co-overexpression were correlated with a worsened OS (P=0.007). Conclusions: EZH2 was an independent negative prognostic biomarker for luminal subtype breast cancer. Targeting HIF-1α transcriptionally regulated EZH2 pathway might be of benefit in the treatment of luminal subtype of breast cancer.

scholarly journals PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2742
Author(s):  
Ramona Erber ◽  
Julia Meyer ◽  
Helge Taubert ◽  
Peter A. Fasching ◽  
Sven Wach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Subtypes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Cancer Subtypes ◽  
Prognostic Effect ◽  
Enhanced Expression ◽  
Disease Free

PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.

Elevated preoperative serum level of tumor markers CEA and CA 15–3 in breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 621-621
Author(s):  
B. Park ◽  
H. Kim ◽  
J. Oh ◽  
S. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Tumor Size ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Metastases ◽  
Disease Free

621 Background: Serological tumor markers: Cancer Antigen 15–3 (CA 15–3), Carcinoembryonic Antigen (CEA), have been investigated as useful markers for monitoring of response to treatment and for predicting outcome in breast cancer patients. Methods: A total of 820 breast cancer patients, treated over the period April 1999 through December 2003, had preoperative CA15–3 and CEA concentrations measured. The stage of the primary tumor ranged from 0 to IV. The median age of the patients was 47years (range 20–88 years old). The concentration of markers was investigated with regard to clinico-pathological parameters and patients outcome by both univariate and multivariate analysis. We determined the range of normality by the mean + 2 standard deviations of the markers distribution in populations of healthy females, who took an annual health screening program. Survival curves for disease free survival and death from disease were estimated by the method of Kaplan-Meier method and differences between groups in survival were tested using the log-rank test. All statistical analyses were carried out using SPSS statistics software (ver 10.5). Results: Among 820 patients, elevated preoperative level of CA15–3 and CEA was identified in 100 (12.2%) and 83 (10.1%) patients, respectively. Tumor size (>5cm), lymph node metastases (≥4), advanced stage (stage III and IV) were associated with significantly higher level of both preoperative CA15–3 and CEA. Elevated preoperative values of CA15–3 and CEA were associated with poor disease free survival (DFS, p=0.0019, p=0.0001, respectively) and distant relapse-free survival (DRFS, p=0.011, p=0.0034), but the level was marginal for overall survival (OS, p=0.0848, p=0.0895). By Cox’s multivariate analysis, younger age (<35 years), larger tumor size(>2cm), axillary node metastases, negative ER expression, elevated preoperative values of CA15–3 and CEA were independent prognostic factors for DFS and DRFS. Conclusions: High level of preoperative CA 15–3 and CEA might reflect a tumor burden, and is associated with advanced disease condition and disease-free survival. Measuring preoperative levels of CA 15–3 and CEA might be helpful for predicting the outcome and for planning the adjuvant therapy in breast cancer patients. No significant financial relationships to disclose.

scholarly journals The Prognostic Value of Intermedin in Patients with Breast Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yi-Min Lu ◽  
Jian-Bo Zhong ◽  
Hai-Yong Wang ◽  
Xiong-Fei Yu ◽  
Zhong-Qi Li
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Adverse Event ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects usingt-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer.

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

scholarly journals Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 511 ◽  
Author(s):  
Viktor Hlavac ◽  
Maria Kovacova ◽  
Katerina Elsnerova ◽  
Veronika Brynychova ◽  
Renata Kozevnikovova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Cytotoxic Therapy ◽  
Free Survival ◽  
Testing Phase ◽  
Major Allele Frequency ◽  
Set Up ◽  
Disease Free

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASPTM technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized.

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