scholarly journals A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients

2018 ◽  
Author(s):  
Hoa Quynh Tran ◽  
Phuc Loi Luu ◽  
Van Thai Than ◽  
Declan Clarke ◽  
Hanh Ngoc Lam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Endocrine Resistance ◽  
Low Risk ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Survival Times ◽  
Free Survival

AbstractASMT is a key determinant of the levels of released melatonin. Though melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles from thousands of patients and found thatASMTexpression was significantly lower in breast cancer tumors relative to healthy tissue. Among cancer patients, those with greater expression had better relapse-free survival outcomes and longer metastasis-free survival times, and they also experienced longer periods before relapse or distance recurrence following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promoted cancer cell death by promoting apoptosis. Motivated by these results, we devised an ASMT gene signature that identifies low-risk cases with great accuracy. This signature was validated using both mRNA array and RNAseq datasets. Intriguingly, patients who are classified as high-risk benefit from adjuvant chemotherapy, and those with grade II tumors who are classified as low-risk exhibit improved overall survival and distance relapse-free outcomes following endocrine therapy. Our findings more clearly elucidate the roles ofASMT,provide strategies for improving the efficacy of tamoxifen treatment, and help to identify those patients who may maximally benefit from adjuvant or endocrine therapies.

Impact of the EndoPredict-clin score on risk stratification in ER-positive, HER2-negative breast cancer after considering clinical guidelines.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 542-542
Author(s):  
Martin Filipits ◽  
Peter Christian Dubsky ◽  
Margaretha Rudas ◽  
Jan C. Brase ◽  
Ralf Kronenwett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Guidelines ◽  
Risk Groups ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Er Positive

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two randomized phase III trials (Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with endocrine therapy only. Results: Although all analyzed clinical guidelines identified a low-risk group with improved metastasis-free survival, the overwhelming majority of all patients (81-94%) were classified as intermediate / high risk. In contrast to that, the EPclin classified only 37% of all patients as high risk and that stratification resulted in the best separation between low and high risk groups (p < 0.001, HR = 5.11 (3.48-7.51). Consequently, the majority of all patients deemed intermediate / high risk by the clinical guidelines was re-classified as low risk by the EPclin score. Kaplan Meier analyses demonstrated that the re-classified subgroups (47 to 57% of all patients) had an excellent 10-year metastasis-free survival of 95% comparable to the clinical assigned low-risk groups although encompassing a higher proportion of the trial patients. Conclusions: The EPclin score predicted distant recurrence more accurately than all three clinical guidelines and is especially useful to reclassify patients considered as intermediate / high risk by the guidelines. The data suggests that the EPclin score provides clinically useful prognostic information beyond common clinical guidelines and can be used to accurately identify the clinically relevant group of patients who are adequately and sufficiently treated with adjuvant endocrine therapy alone.

scholarly journals AGR2 Predicts Tamoxifen Resistance in Postmenopausal Breast Cancer Patients

2013 ◽  
Vol 35 ◽  
pp. 207-212 ◽  
Author(s):  
Roman Hrstka ◽  
Veronika Brychtova ◽  
Pavel Fabian ◽  
Borivoj Vojtesek ◽  
Marek Svoboda
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Optimal Algorithm ◽  
Endocrine Resistance ◽  
Postmenopausal Breast Cancer ◽  
Progression Free Survival ◽  
Tamoxifen Treatment ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Er Positive

Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients. Our results showed inversed association of AGR2 mRNA levels with primary treatment response (P=0.0011) and progression-free survival (P=0.0366) in 61 ER-positive breast carcinomas. As shown by our experimental and clinical evaluations, elevated AGR2 expression predicts decreased efficacy of tamoxifen treatment. From this perspective, AGR2 is a potential predictive biomarker enabling selection of an optimal algorithm for adjuvant hormonal therapy in postmenopausal ER-positive breast cancer patients.

scholarly journals A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease‐free survival in low‐risk breast cancer patients

2019 ◽  
Vol 110 (5) ◽  
pp. 1695-1704 ◽  
Author(s):  
Iveta Zmetakova ◽  
Lenka Kalinkova ◽  
Bozena Smolkova ◽  
Viera Horvathova Kajabova ◽  
Zuzana Cierna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free ◽  
Risk Breast Cancer

scholarly journals Identification and Validation of a Five-Gene Signature Associated With Overall Survival in Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaolong Wang ◽  
Chen Li ◽  
Tong Chen ◽  
Wenhao Li ◽  
Hanwen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Risk Model ◽  
Expression Profiles ◽  
External Validation ◽  
Gene Signature ◽  
Breast Cancer Patients ◽  
Study Gene Expression

BackgroundRecent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand.ResultsIn this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression.ConclusionsWe established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.

Sequential Tamoxifen and Aminoglutethimide Versus Tamoxifen Alone in the Adjuvant Treatment of Postmenopausal Breast Cancer Patients: Results of an Italian Cooperative Study

2001 ◽  
Vol 19 (22) ◽  
pp. 4209-4215 ◽  
Author(s):  
F. Boccardo ◽  
A. Rubagotti ◽  
D. Amoroso ◽  
M. Mesiti ◽  
D. Romeo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Tamoxifen Group

PURPOSE: To determine whether switching patients from tamoxifen to antiaromatase treatment would prevent some of the relapses or deaths that we assume would occur if tamoxifen were continued. PATIENTS AND METHODS: Three hundred eighty postmenopausal breast cancer patients receiving adjuvant tamoxifen treatment for 3 years were randomized to either continue tamoxifen for 2 more years or to switch to low-dose aminoglutethimide (250 mg daily) for 2 years. RESULTS: At a median follow-up of 61 months (range, 5 to 94 months), 59 events occurred in the tamoxifen group, and 55 occurred in the aminoglutethimide group. More treatment failures at distant sites, such as viscera (P = .02), were observed in the tamoxifen group. Although no differences in disease-free survival between the two groups have emerged so far, a significant trend favors aminoglutethimide in overall survival (P = .005) and breast cancer–specific survival (P = .06). Even if more patients in the antiaromatase group complained of drug-related side effects and more of them discontinued treatment (P = .0001), the number of cardiovascular events and, in general, of life-threatening adverse events was higher in the tamoxifen arm. CONCLUSION: Switching patients from tamoxifen to aminoglutethimide treatment resulted in comparable event-free survival, but longer overall survival was achieved in patients who were switched to aminoglutethimide as compared with those who continued to receive tamoxifen. Should these preliminary results be confirmed by larger studies with a similar design, which are now testing the effectiveness of the new, more active, and tolerable aromatase inhibitors, sequencing tamoxifen with an aromatase inhibitor could become a preferable alternative to tamoxifen alone in early breast cancer patients.

scholarly journals Association of Mammographic Density Reduction with Hormone Therapy and Relapse in Asian Breast Cancer Patients: A Multivariate Survival Analysis

2021 ◽  
Author(s):  
Wei-Chung Shia ◽  
Hwa-Koon Wu ◽  
Li-Sheng Lin ◽  
Dar-Ren Chen
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Cancer Patients ◽  
Mammographic Density ◽  
Endocrine Resistance ◽  
Disease Free Survival ◽  
Mammographic Breast Density ◽  
Breast Cancer Patients ◽  
Free Survival

Abstract Purpose Currently, the ability to predict the development of resistance to hormone therapy (HT) in breast cancer patients is suboptimal, and attempts are ongoing to develop more specific prognostic markers for endocrine resistance. Several studies have shown that mammographic breast density is an important predictor of outcomes following adjuvant HT. This study aimed to evaluate HT-induced mammographic density (MD) reduction (MDR) and its association with relapse and metastasis in Taiwanese patients.MethodsIn this retrospective study conducted at the Changhua Christian Hospital, 1553 breast cancer patients were screened. Of these, 399 with luminal-like cancer who were first diagnosed between January 2011 and December 2017 and had received adjuvant HT (include treatment with tamoxifen, aromatase inhibitor or mixture) were enrolled. The mean follow-up period for all patients was 1847 days (median follow-up period was 1815 days). The MD was measured as a percentage using the automatic volumetric mammographic density estimation.ResultsWe found the MDR equally 20.8% which MD measured was before and after surgery and HT during 6 to 18 months was a significant cut-off threshold for good or pool diagnosis in breast cancer patients who receiving HT. By utilized the Cox proportion-hazards model analysis, the disease-free survival rate was significantly higher in MDR-positive patients (MDR > 20.8%) than in MDR-negative patients (MDR < 20.8%) (p = 0.048). Age, histologic grade, histologic stage, and lymph node metastasis showed a significant association with recurrence-free survival in all patients.ConclusionsOur results demonstrate the feasibility of using MDR to predict the preliminary outcomes of adjuvant HT in Asian breast cancer patients.

scholarly journals Integrated Analysis Revealed Hub Genes in Breast Cancer

2018 ◽  
Author(s):  
Haoxuan Jin ◽  
Xiaoyan Huang ◽  
Kang Shao ◽  
Guibo Li ◽  
Jian Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Network Analysis ◽  
Cancer Patients ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Integrated Analysis ◽  
Breast Cancer Patients ◽  
Survival Times ◽  
Hub Genes

AbstractThe aim of this study was to identify the hub genes in breast cancer and provide further insight into the tumorigenesis and development of breast cancer. To explore the hub genes in breast cancer, we performed an integrated bioinformatics analysis. Two gene expression profiles were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by using the “limma” package. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional annotation and potential pathways of the DEGs. Next, protein–protein interaction (PPI) network analysis and weighted gene coexpression network analysis (WGCNA) were conducted to screen for hub genes. To confirm the reliability of the identified hub genes, we obtained TCGA-BRCA data by using WGCNA to screen for genes that were strongly related to breast cancer. By combining the results from the GEO and TCGA datasets, we finally identified 15 real hub genes in breast cancer. Finally, we performed an overall survival analysis to explore the connection between the expression of hub genes and the overall survival time of breast cancer patients. We found that for all hub genes, higher expression was associated with significantly shorter overall survival times among breast cancer patients.

scholarly journals Profiles of ferroptosis-related genes and their prognostic values in patients with breast cancer brain metastasis

2021 ◽  
Author(s):  
Lei Zhu ◽  
Mu Chen ◽  
Bingsong Huang ◽  
Min Liu ◽  
Chunlong Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Risk Group ◽  
Expression Profiles ◽  
Low Risk ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Breast Cancer Brain Metastasis

Abstract Background Ferroptosis is involved in various cancers. The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) expression profiles in BCBM, as well as evaluate the FRG prognostic values in breast cancer patients.Methods Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Functional enrichment analysis was used to investigate the FRG bioinformatics functions. Univariate and multivariate cox regression analysis were performed to explore the independent prognostic factors. The correlation between ferroptosis and immunity was also evaluated. Finally, the FRG and their prognostic values were validated in external cohorts.Results Fourteen significantly different FRG were screened between breast cancer and BCBM tissues. GO and KEGG results showed FRG were enriched in the ferroptosis-related activities. Protein‑protein interaction (PPI) network analysis showed the HMOX1 and TFRC were hub genes. Survival analysis demonstrated HMOX1 and PEBP1 were significantly associated with overall survival (OS) (HR=2.100, P=0.035; HR=0.421, P=0.017 respectively). The KEAP1 and LPCAT3 had prognostic values for relapse-free survival (RFS) (HR=0.745, P=0.002; HR=2.536, P=0.008 respectively). Patients in high-risk group have worse OS and RFS compared with those in low-risk group (P=0.004, 0.021 respectively). Clinical correlation analysis revealed FRG were significantly associated with estrogen receptor (ER) status, progesterone receptor (PgR) status, HER2 and pathological grade in breast cancer patients (all P<0.05). In addition, we also found that immune-related pathways and immune status were different between high and low-risk groups. External cohort results showed FRG were significantly different between breast cancer and BCBM tissues. Survival validation demonstrated ALOX5 and CS were associated with prognosis in breast cancer patients (P=0.044, 0.032 respectively). Conclusions Our study identified the ferroptosis-related genes that may be involved in biology of BCBM, and FRG could serve as prognostic biomarkers in breast cancer patients. New therapy targeting ferroptosis holds probabilities for effective treatment in BCBM patients.

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