Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: a systematic review

2018 ◽  
Vol 56 (5) ◽  
pp. 688-701 ◽  
Author(s):  
Ina Mathilde Kjaer ◽  
Troels Bechmann ◽  
Ivan Brandslund ◽  
Jonna Skov Madsen
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Predictive Value ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Current Evidence ◽  
Breast Cancer Patients ◽  
Baseline Serum ◽  
Egfr Ligands

AbstractEpidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR-inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments. The aim is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review was conducted in accordance to the PRISMA guidelines. Literature searches were conducted to identify publications exploring correlations between EGFR/EGFR-ligands in serum/plasma of breast cancer patients and prognostic/predictive outcome measures. Sixteen publications were eligible for inclusion. Twelve studies evaluated EGFR, whereas five studies evaluated one or more of the EGFR-ligands. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced breast cancer, especially in patients with estrogen and/or progesterone receptor positive tumors. The prognostic and predictive value of EGFR and EGFR-ligands in blood has only been investigated in highly selected subsets of breast cancer patients and most studies were small. This is the first systematic review evaluating the utility of EGFR and EGFR-ligands as predictive and prognostic biomarkers in blood in breast cancer. Further exploration in large well-designed studies is needed.

scholarly journals Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Expression Patterns ◽  
Survival Rates ◽  
In Silico Analysis ◽  
Cancer Prognosis ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Non Coding Rnas

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

scholarly journals Diagnostic Value of Serum HER2 Levels in Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Amir Shamshirian ◽  
Amir Reza Aref ◽  
George W. Yip ◽  
Majid Ebrahimi Warkiani ◽  
Keyvan Heydari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Meta Analysis ◽  
Breast Cancer Patients ◽  
Diagnostic Screening ◽  
Her 2 ◽  
Low Sensitivity

Abstract Background:Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.Methods:We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).Results:Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82-65.28), but reasonable specificity of 79.27 (95%CI 73.02-85.51), accuracy of 72.06 (95%CI 67.04-77.08) and AUC of 0.79 (95%CI 0.66-0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16-68.20), NPV (NPV: 76.93, 95%CI 69.56-84.31), PLR (PLR: 2.10, 95%CI 1.69-2.50) and NLR (NLR: 0.58, 95%CI 0.44-0.71).Conclusion:Our findings revealed that although serum HER-2 levels showed low sensitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

scholarly journals The Risk of Psychological Stress on Cancer Recurrence: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5816
Author(s):  
Hyeon-Muk Oh ◽  
Chang-Gue Son
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cohort Studies ◽  
Cancer Patients ◽  
Psychological Stress ◽  
Cancer Recurrence ◽  
Current Evidence ◽  
Cochrane Library ◽  
Breast Cancer Patients ◽  
Data Points

Cancer recurrence is a significant clinical issue in cancer treatment. Psychological stress has been known to contribute to the incidence and progression of cancer; however, its effect on cancer recurrence remains inconclusive. We conducted a systematic review to examine the current evidence from the Medline (PubMed), Embase and Cochrane Library up to May 2021. Among 35 relevant articles, a total of 6 studies (10 data points) were finally selected, which enrolled 26,329 patients (26,219 breast cancer patients except hepatocellular carcinoma patients in 1 study), 4 cohort studies (8 data points) and 2 RCTs (2 data points). Among the 8 data points in cohort studies, four psychological stress-related factors (two ‘anxiety’, one ‘depression’, and one ‘hostility’) were shown to be moderately related with the risk for cancer recurrence, while ‘loss of partner’ resulted in opposite outcomes. The ‘emotional‘ and ‘mental’ health factors showed conflicting results, and an RCT-derived meta-analysis proved the positive efficiency of psychotherapies in reducing the cancer recurrence risk among breast cancer patients (HR = 0.52; 95% CI 0.33–0.84). Despite the limitations, this study produces comprehensive information about the effect of psychological stress on cancer recurrence and provides reference data to clinicians and scientists for further studies.

scholarly journals Diagnostic Value of Serum HER2 Levels in Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Amir Shamshirian ◽  
Amir Reza Aref ◽  
George W. Yip ◽  
Majid Ebrahimi Warkiani ◽  
Keyvan Heydari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Meta Analysis ◽  
Breast Cancer Patients ◽  
Diagnostic Screening ◽  
Her 2 ◽  
Low Sensitivity

Abstract Background: Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict of prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.Methods: We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).Results: Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82-65.28), but reasonable specificity of 79.27 (95%CI 73.02-85.51) and accuracy 72.06 (95%CI 67.04-77.08). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16-68.20), NPV (NPV: 76.93, 95%CI 69.56-84.31), PLR (PLR: 2.10, 95%CI 1.69-2.50) and NLR (NLR: 0.58, 95%CI 0.44-0.71).Conclusion: Our findings revealed that although serum HER-2 levels showed low sensitivity for breast cancer diagnosis, its specificity was reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

scholarly journals Diagnostic value of serum HER2 levels in breast cancer: a systematic review and meta-analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Amir Shamshirian ◽  
Amir Reza Aref ◽  
George W. Yip ◽  
Majid Ebrahimi Warkiani ◽  
Keyvan Heydari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Breast Cancer Patients ◽  
Diagnostic Screening ◽  
Her 2

Abstract Background Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods. Methods We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Results Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82–65.28), but reasonable specificity of 79.27 (95%CI 73.02–85.51), accuracy of 72.06 (95%CI 67.04–77.08) and AUC of 0.79 (95%CI 0.66–0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16–68.20), NPV (NPV: 76.93, 95%CI 69.56–84.31), PLR (PLR: 2.10, 95%CI 1.69–2.50) and NLR (NLR: 0.58, 95%CI 0.44–0.71). Conclusion Our findings revealed that although serum HER-2 levels showed low se nsitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

scholarly journals Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: a protocol for a systematic review and network meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e033461
Author(s):  
Kyeore Bae ◽  
Si Yeon Song
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Pain Intensity ◽  
Aromatase Inhibitor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Indirect Evidence ◽  
Secondary Outcome ◽  
Breast Cancer Patients ◽  
Patient Reported

IntroductionAromatase inhibitor-induced arthralgia (AIA) is a major adverse event of aromatase inhibitors (AIs) and leads to premature discontinuation of AI therapy in breast cancer patients. The objective of this protocol for a systematic review and network meta-analysis (NMA) is to provide the methodology to compare the change in pain intensity between different AIA treatments and demonstrate the rank probabilities for different treatments by combining all available direct and indirect evidence.Methods and analysisPubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE, Web of Science and ClinicalTrials.gov will be searched to identify publications in English from inception to November 2019. We will include randomised controlled trials (RCTs) assessing the effects of different treatments for AIA in postmenopausal women with stage 0–III hormone receptor-positive breast cancer. The primary endpoints will be the change in patient-reported pain intensity from baseline to post-treatment. The number of adverse events will be presented as a secondary outcome.Both pairwise meta-analysis and NMA with the Frequentist approach will be conducted. We will demonstrate summary estimates with forest plots in meta-analysis and direct and mixed evidence with a ranking of the treatments as the P-score in NMA. The revised Cochrane risk-of-bias tool for randomised trials will be used to assess the methodological quality within individual RCTs. The quality of evidence will be assessed.Ethics and disseminationAs this review does not involve individual patients, ethical approval is not required. The results of this systematic review and NMA will be published in a peer-reviewed journal. This review will provide valuable information on AIA therapeutic options for clinicians, health practitioners and breast cancer survivors.PROSPERO registration numberCRD42019136967.

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

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