scholarly journals Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3756
Author(s):  
Alaleh Zati zehni ◽  
Falk Batz ◽  
Vincent Cavaillès ◽  
Sophie Sixou ◽  
Till Kaltofen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protective Factor ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tnm Staging ◽  
Clinicopathological Parameters ◽  
Tissue Samples ◽  
Free Survival ◽  
Poor Outcomes ◽  
Independent Marker

The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

scholarly journals Potential prognostic value of PD-L1 and FOXP3 as predictors of relapse in breast cancer

2019 ◽  
Vol 9 (2) ◽  
pp. 38
Author(s):  
Reham Nagib ◽  
Sherine Refat ◽  
Ahmed E. Eladl ◽  
Ziad Emarah ◽  
Khaled Elnaghi
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Treg Cells ◽  
Clinicopathological Parameters ◽  
Advanced Stage ◽  
Breast Cancer Patients ◽  
Duct Carcinoma ◽  
Free Survival ◽  
Cancer Management

Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p = .003), basal-like subtype(p = .001), high Ki67(p = .001), negative ER status(p = .001), negative PR(p = .028), HER2 expression(p = .04), advanced stage (p = .001), and LN metastases(p = .001). For PDL1, only statistically significant correlation with high Ki67 (p = .018) and advanced stage(p = .03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p= .001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p = .054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.

scholarly journals Validation of the GenesWell BCT Score in Young Asian Women With HR+/HER2− Early Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mi Jeong Kwon ◽  
Jai Min Ryu ◽  
Soo Youn Cho ◽  
Seok Jin Nam ◽  
Seok Won Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Predictive Value ◽  
Age Groups ◽  
Young Patients ◽  
Disease Free Survival ◽  
Low Risk ◽  
Tissue Samples ◽  
Free Survival ◽  
Her2 Breast Cancer

BackgroundThe prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group.MethodsWe identified patients with pN0-1, HR+/HER2− breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score.ResultsA total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged >50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05–1.56; P = 0.015), as well as those aged >50 years.ConclusionThe BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2− early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.

scholarly journals TTK Predicts Triple Positive Breast Cancer Prognosis and Regulates Tumor Proliferation and Invasion

2021 ◽  
Author(s):  
Yunhe Gao ◽  
Shanshan Qu ◽  
Lanqing Cao ◽  
Min Yao
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Spindle Assembly Checkpoint ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free ◽  
Positive Breast Cancer

Abstract Background: This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. Methods: We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan–Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. Results: The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29–86 years). TTK expression was positively correlated with tumor size (P = 0.034), p53 status (P = 0.023), TNM stage (P = 0.023), and Ki-67 index (P< 0.001). The Kaplan–Meier curves revealed that TTK expression was correlated with poor disease-free survival (P = 0.001) and overall survival (P = 0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (P = 0.007 and P = 0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. Conclusions: The findings of the study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK may serve as a prognostic marker for TPBC.

scholarly journals Clinicopathological Significance of TARBP2, APP, and ZNF395 in Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40820
Author(s):  
Ryoko Oi ◽  
Hirotaka Koizumi ◽  
Ichiro Maeda ◽  
Akira Noguchi ◽  
Shinobu Tatsunami ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Expression Levels ◽  
Node Metastasis ◽  
Disease Free

The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.

scholarly journals A Novel Automated Immunoassay Platform to Evaluate the Association of Adiponectin and Leptin Levels with Breast Cancer Risk

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3303
Author(s):  
Debora Macis ◽  
Valentina Aristarco ◽  
Harriet Johansson ◽  
Aliana Guerrieri-Gonzaga ◽  
Sara Raimondi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cox Model ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Baseline Serum ◽  
Free Survival ◽  
Disease Free

Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing–Bablok regression and Bland–Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, p = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

scholarly journals Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

2021 ◽  
Author(s):  
Wanting Shao ◽  
Christina Kuhn ◽  
Doris Mayr ◽  
Nina Ditsch ◽  
Magdalena Kailuwait ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Poor Prognosis ◽  
Early Stage ◽  
Clinicopathological Characteristics ◽  
Clinicopathological Parameters ◽  
Liver X Receptors ◽  
X Receptors ◽  
Independent Marker ◽  
Overall Survival Analysis

Abstract Purpose The aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival. Methods In a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed. Results LXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumors Conclusion Altogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC.

scholarly journals Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solene De Talhouet ◽  
Julien Peron ◽  
Aurelie Vuilleumier ◽  
Alex Friedlaender ◽  
Valeria Viassolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Brca1 And Brca2 ◽  
Free Survival ◽  
Entire Cohort ◽  
Dna Damaging Agents ◽  
Impact On Survival ◽  
Brca1 Brca2 ◽  
Brca1 And Brca2 Mutations

Abstract BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44–0.90 for BRCA1; HR = 0.72; 95%CI, 0.47–1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40–1.1 for BRCA1; HR = 0.78; 95%CI, 0.44–1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28–0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11–1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21–0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11–1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.

Sign in / Sign up

Export Citation Format

Share Document