Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Giovana F Piccoli ◽  
Leonardo A Mesquita ◽  
Cinara Stein ◽  
Marina Aziz ◽  
Maira Zoldan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Neoplasms ◽  
Sequential Analysis ◽  
Data Extraction ◽  
Meta Analysis ◽  
Development Program ◽  
Trial Sequential Analysis ◽  
Obesity And Diabetes ◽  
Risk Of Cancer

Abstract Context Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. Objective To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Data Sources We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. Study Selection Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. Data Extraction Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Data Synthesis We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76–1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48–2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusions Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.

scholarly journals Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-Analysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A352-A353
Author(s):  
Giovana Fagundes Piccoli ◽  
Leonardo A Mesquita ◽  
Cinara Stein ◽  
Marina M Aziz ◽  
Maira Zoldan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Breast Neoplasms ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Development Program ◽  
Trial Sequential Analysis ◽  
Obesity And Diabetes ◽  
Risk Of Cancer

Abstract Background: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the liraglutide development program, a glucagon-like peptide-1 receptor agonist (GLP-1RA), subjects treated with the active drug had a higher absolute number of breast cancer events. Aim: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Methods: We searched MEDLINE, Embase, Web of Science, and CENTRAL from inception to February 8, 2020. Three pairs of reviewers examined and retrieved abstractsand full-text articles for RCTs of GLP-1RAs versus non-GLP-1RA controls(active or placebo) in adults with overweight, obesity, prediabetes, or diabetes,with a minimum follow-up period of 24 weeks and which reported at least oneevent of breast cancer or benign breast neoplasm. Divergences were dealt withby consensus. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. This study follows PRISMA reporting guidelines. Results: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48267 subjects treated with GLP-1RAs, 130 developed breast cancer compared to 107 of 40755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76 to 1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48 to 2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusion: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms. Register: This systematic review was preregistered in PROSPERO (CRD42019132704).

scholarly journals Clinical Effectiveness and Safety of Chinese Herbal Medicine Compound Kushen Injection as an Add-On Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Bao-Yong Lai ◽  
Ai-Jing Chu ◽  
Bo-Wen Yu ◽  
Li-Yan Jia ◽  
Ying-Yi Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sequential Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Objective Response ◽  
Trial Sequential Analysis ◽  
Karnofsky Performance Scale ◽  
Improvement Rate ◽  
Score Improvement ◽  
Compound Kushen Injection

Objective. To systematically evaluate the effect and safety of compound Kushen injection (CKI) as an add-on treatment on the treatment for breast cancer. Methods. We searched eight major electronic databases from their inception to November 1, 2021, for randomized clinical trials (RCTs) comparing CKI plus chemotherapy with chemotherapy alone. Primary outcomes included objective response rate (ORR) and disease control rate (DCR), health-related quality of life (HRQoL), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse drug reactions (ADRs) and tumor marker level. We used Cochrane’s RevMan 5.3 for data analysis. The GRADEpro was used to appraise the certainty of evidence. Trial sequential analysis (TSA) was applied to estimate the required sample size in a meta-analysis and test the robustness of the current results. Results. Thirty RCTs with 2556 participants were totally included. CKI plus chemotherapy showed significant effects in increasing ORR (RR 1.30, 95%CI [1.18, 1.43], I2 = 27%, n = 1694), increasing DCR (RR 1.21, 95%CI [1.15, 1.28], I2 = 16%, n = 1627), increasing HRQol as measured by Karnofsky Performance Scale (KPS) score improvement rate (RR 1.42, 95% CI [1.26, 1.61], I2 = 37%, n = 1172), increasing the PFS (MD 2.24 months, 95%CI [1.26, 3.22], n = 94) and the OS (MD 2.24 months, 95%CI [1.45, 3.43], n = 94), compared to chemotherapy alone. The results showed that CKI plus chemotherapy had a lower risk of ADRs than that of chemotherapy alone group. The certainty of evidence of the included trials was generally low to very low. TSA for ORR and KPS score improvement rate demonstrated that the current results reached a sufficient power regarding both numbers of trials and participants. Conclusions. Low certainty of evidence suggested that the combination of CKI and conventional chemotherapy appeared to improve ORR, DCR, and KPS score in breast cancer patients. Conclusions about PFS and OS could not be drawn due to lack of evidence. Additionally, CKI appeared to relieve the risk of ADRs in patients with breast cancer receiving chemotherapies. However, due to weak evidence, the findings should be further confirmed in large and rigorous trials.

scholarly journals PARP inhibitor treatment of advanced breast cancer beyond the BRCA-mutated type: a meta-analysis

2021 ◽  
Author(s):  
Feifei Yan ◽  
Qi Jiang ◽  
Mengye He ◽  
Peng Shen
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Sequential Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Parp Inhibitors ◽  
Advanced Breast ◽  
Trial Sequential Analysis

Background: We conducted this meta-analysis to compare the efficacy and safety of PARP inhibitors with or without chemotherapy versus chemotherapy alone for advanced breast cancer. Methods: A meta-analysis and trial sequential analysis were performed using RevMan 5.2 analysis software. Results: Six eligible randomized clinical trials involving 2080 patients were included. Regimens containing PARP inhibitors were significantly associated with higher objective response rate, longer progression-free survival and overall survival. The PARP inhibitor regimen group had a significantly higher rate of grade ≥3 thrombocytopenia than the chemotherapy-only group. Conclusion: Regimens containing PARP inhibitors are effective and safe for BRCA-mutated advanced breast cancer patients. The efficacy appears to be only marginal in patients with BRCA status unselected.

scholarly journals Nutritional Status in Patients with Acute heart failure: A systematic review and meta-analysis with trial sequential analysis

2021 ◽  
Author(s):  
Jihane Belayachi ◽  
Imane Katir ◽  
Rhita Nechba Bennis ◽  
Naoufel Madani ◽  
Redouane Abouqal
Keyword(s):  
Heart Failure ◽  
Nutritional Status ◽  
Quality Assessment ◽  
Publication Bias ◽  
Acute Heart Failure ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
All Cause Mortality

AbstractA critical review of the prognosis impact of malnutrition in patients admitted with acute heart failure (AHF) has never been performed. We systematically reviewed the observational epidemiology literature to determine the all-cause mortality (ACM) in undernourished patients with acute heart failure or at risk of malnutrition through a meta-analysis of observational studies.A systemic search using PubMed, Scopus, and Web of Science was done for articles reporting an association between malnutrition and mortality in patient with acute heart failure published before December 2019. Original data from observational cohort studies in patients with acute heart failure at baseline, and with nutritional state evaluation at admission using screening, or assessment tools. The outcome of interest was mortality independent of the timeframe for follow up. The characteristics of the included study were collected. Data quality assessment using the Newcastle Ottawa Quality Assessment Scale. The hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted. For the meta-analysis, a random-effects model was considered.Heterogeneity between studies was assessed using Cochran Q statistics and I2 statistics. Subgroup analyses were used to identify the source of heterogeneity. A sensitive analysis was performed to reflect the influence of the individual data set on the pooled HR. Publication bias was detected using the Doi plot and Luis Furuya-Kanamori asymmetry index (LFK index). The influence of potential publication bias on results was explored by using the trim-and-fill procedure. To assess the risks of random errors, trial sequential analysis (TSA) was performed.Seven studies were eligible for review and meta-analysis. There were 9053 participants and over 1536 events occurred. The prevalence of malnutrition varied from 33% to 78.8%. Mean follow-up varied between 189 and 951 days. ACM rates varied between 7% and 42.6%. Nutritional status is significantly associated with mortality in patients with AHF (Pooled HR=1.15;95%CI[1.08-1.23]). Considerable between-study heterogeneity was observed (I2=83%, P=0.001). Heterogeneity was partially explained by the different tools used to screen malnutrition risk, and follow-up durations used by the included studies. There was evidence of major publication bias regarding the risk of malnutrition-related to ACM. The obtained LFK index was 6.12 and suggests major asymmetry. The recalculated pooled HR that incorporates the hypothetical missing studies is 1.15; 95%CI (1.08-1.22). However, the accumulating number of participants and the required information size has not yet been achieved. Then, the trial sequential monitoring boundary is inconclusive.This first meta-analysis of the association between nutritional status in patients with acute heart failure and all-cause mortality indicated that malnutrition risk in a patient with acute heart failure was associated with increased all-cause mortality. The prognosis impact of malnutrition is real despite heterogeneity in tools and cut off for defining malnutrition and mean follow up duration. This review underlines the peremptory need for multicenter studies, for uniform guidelines for assessing nutritional status, and for reporting guidelines for prognostic studies in an acute cardiovascular setting. Better nutritional practice to improve patient care is emphasized in international and national health care guidelines.

scholarly journals Relationship between Aurora-A V57I Polymorphism and the Risk of Cancer: A Meta-Analysis and Trial Sequential Analysis

2020 ◽  
Vol 11 (11) ◽  
pp. 3225-3234
Author(s):  
Guangyuan Chen ◽  
Cong Hu ◽  
Yuxuan Song ◽  
Mengxi Xiu ◽  
Yiling Zhang ◽  
...  
Keyword(s):  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Aurora A ◽  
Risk Of Cancer

scholarly journals Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis

2021 ◽  
Vol 20 ◽  
pp. 153473542110638
Author(s):  
Ya Wen Shih ◽  
Jui Yuan Su ◽  
Yu Shan Kung ◽  
Yu Huei Lin ◽  
Duong Thi To Anh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Random Effects ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
White Blood Cells ◽  
Cochrane Library ◽  
Common Side Effect ◽  
Trial Sequential Analysis ◽  
Random Effects Model

Background: Breast cancer is one of the most common cancers and a major cause of death in women worldwide. Chemotherapy is mainly used to treat and control the progression of breast cancer. Leukopenia is the most common side effect of chemotherapy which may decrease immune function and further lead to serious fatal infections. The purpose of this study was to evaluate the effect of acupuncture on regulating hematopoietic function in chemotherapy-induced leukopenia among patients with breast cancer. Methods: PubMed, Embase, Cochrane Library, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure (CNKI) databases were searched to August 2021 for papers to include in a systematic review and meta-analysis. A random-effects model was applied. The effect size was calculated by Hedges’ g. Heterogeneity was determined using Cochran’s Q test. Moderator analyses were performed to examine potential sources of heterogeneity. A trial sequential analysis (TSA) was conducted to determine whether the current sample size was sufficient. Results: Ten randomized controlled trials involving 650 participants were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leukopenia during chemotherapy. Levels of white blood cells (WBCs) were increased (Hedges’ g = 0.70, P < .001, I2 = 34%), neutrophil counts (Hedges’ g = 0.80, P < .001, I2 = 0%) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased. Conclusions: The current meta-analysis supports acupuncture possibly ameliorating chemotherapy-induced leukopenia, as WBC and neutrophil values significantly increased after acupuncture in patients undergoing chemotherapy. Additionally, regardless of the type of acupuncture, values of WBCs increased. These findings are actionable and support both the clinical use of acupuncture to relieve chemotherapy-induced leukopenia and further research regarding the use of acupuncture in patients experiencing immunosuppression when undergoing chemotherapy. Trial Registration: PROSPERO-CRD42020215759.

scholarly journals Drug-Coated Balloon Angioplasty and Debulking for the Treatment of Femoropopliteal In-Stent Restenosis: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Zhu Tong ◽  
Lianrui Guo ◽  
Lixing Qi ◽  
Shijun Cui ◽  
Xixiang Gao ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Balloon Angioplasty ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Cochrane Central Register ◽  
Stent Restenosis ◽  
Drug Coated Balloon ◽  
In Stent Restenosis

The purpose of this article was to compare the efficiency and safety of drug-coated balloon angioplasty (DCB) and atherectomy with percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal in-stent restenosis (ISR). Pubmed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) (all up to March 2019) were searched systematically. Trial sequential analysis (TSA) was conducted. 5 studies with 599 participants were included. Compared with PTA, DCB significantly increased the rate of patency (6 months: RR 1.65, 95% CI 1.30 to 2.09, P<0.01; 12 months: RR 2.38, 95% CI 1.71 to 3.30, P<0.01) and the rate freedom from target lesion revascularization (TLR) (6 months: RR 1.18, 95% CI 1.09 to 1.28, P<0.01; 12 months: RR 1.56, 95% CI 1.33 to 1.82, P<0.01) at 6 and 12 months follow-up, and the TSA results showed these outcomes were reliable. The rate of clinical improvement by ≥1 Rutherford category in the DCB group was higher than that in the PTA group (6 months: RR 1.35, 95% CI 1.03 to 1.75, P=0.03; 12 months: RR 1.46, 95% CI 1.17 to 1.82, P<0.01) at 6 and 12 months. There is no statistically difference of ABI, all-cause mortality, and incidence of amputation between DCB group and PTA group (MD 0.03, 95% CI -0.03 to 0.08, P=0.40; RR 1.24, 95% CI 0.46 to 3.34, P=0.67; RR 0.32, 95% CI 0.01 to 7.61, P=0.48). Compared with PTA, the rate of patency and freedom from TLR in the laser atherectomy (LD) group was higher than that in the PTA group (patency: 6 months: RR 1.28, 95% CI 1.01 to 1.64, P<0.05, 12 months: RR 2.25, 95% CI 1.14 to 4.44, P<0.05; freedom from TLR: 6 months: RR 1.27, 95% CI 1.05 to 1.53, P=0.01, 12 months: RR 1.59, 95% CI 1.12 to 2.25, P=0.01) at 6 and 12 months follow-up. In conclusion, DCB and LD had superior clinical (freedom from TLR and clinical improvement) and angiographic outcomes (patency rate) compared with PTA for the treatment of femoropopliteal ISR. Moreover, DCB and LD had a low incidence of amputation and mortality and were relatively safe methods.

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