scholarly journals Dual HER2 Blockade in Neoadjuvant Treatment of HER2+ Breast Cancer: A Meta-Analysis and Review

2020 ◽  
Vol 19 ◽  
pp. 153303382096072
Author(s):  
Chaokun Wang ◽  
Jing Chen ◽  
Xiangyun Xu ◽  
Xiaochen Hu ◽  
Dejiu Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Cochrane Library ◽  
Her2 Breast Cancer ◽  
Single Target ◽  
Significant Difference ◽  
Dual Target

Background: To investigate the pathologic complete response (pCR) rates of dual human epidermal growth factor receptor 2 (HER2) blockade in a neoadjuvant setting for HER2+ breast cancer. Methods: We searched randomized clinical trials (RCTs) using dual HER2 blockade in a neoadjuvant setting for HER2+ breast cancer in PubMed, the Cochrane Library, Embase and ClinicalTrials.gov up to July 5, 2020, and all included studies were assessed according to the Cochrane Collaboration tool for assessing the risk of bias of RCTs, and the statistical analyses were performed using STATA 14.0 software. Results: A total of 9 RCTs involving 2758 patients were included. Meta-analysis indicated that the pCR rates of lapatinib/pertuzumab/neratinib plus trastuzumab versus trastuzumab [relative risk (RR) = 1.31; 95% confidence interval (CI): 1.21-1.43; p < 0.001)] and lapatinib plus trastuzumab versus lapatinib (RR = 1.39; 95%CI: 1.25-1.53; p < 0.001) showed a significant statistical difference between dual HER2-blockade treatment and single-agent treatment in a neoadjuvant setting for HER2+ breast cancer. Additionally, there was no statistically significant difference in disease-free survival (HR = 0.72; 95% CI: 0.47-1.09; p = 0.123), incidence of serious adverse events (SAEs) (RR = 1.04; 95%CI: 0.81-1.33; p = 0.778) and cardiotoxicity(RR = 1.30; 95%CI: 0.81-2.08; p = 0.280), and the pCR rate was unaffected by hormone receptor status. Conclusions: The pCR rate of neoadjuvant dual-target therapy for HER2+ breast cancer was significantly higher than that of single-target therapy. Furthermore, the results indicated that the safety of dual-target therapy is similar to that of single-target therapy.

scholarly journals Efficacy and safety of neoadjuvant therapy for HER2-positive early breast cancer: a network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Jie Zhang ◽  
Yushuai Yu ◽  
Yuxiang Lin ◽  
Shaohong Kang ◽  
Xinyin Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Combination Chemotherapy ◽  
Target Therapy ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Single Target ◽  
Dual Target ◽  
Better Than ◽  
Positive Breast Cancer

Aims: Currently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints. Methods: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included. Results: A total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that ‘trastuzumab plus pertuzumab’ and ‘T-DM1 containing regimens’ were well balanced in terms of efficacy and toxicity in all target regimens. Conclusion: In summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.

Neoadjuvant dose-dense sequential biweekly epirubicin and cyclophosphamide followed by docetaxel and trastuzumab for HER2+ operable breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 595-595
Author(s):  
L. Blakely ◽  
B. Somer ◽  
M. Keaton ◽  
R. Hermann ◽  
F. Schnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Stage ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Skin Toxicity ◽  
Pathologic Response ◽  
Her2 Breast Cancer ◽  
Grade 3 ◽  
Dose Dense ◽  
Q 14

595 Background: Neoadjuvant (Neo) chemotherapy (CT) with trastuzumab (H) improves pathologic complete response (pCR) rate for HER2+ breast cancer. Dose-dense regimens improve outcome in the adjuvant setting but have not been fully evaluated as preoperative therapy. We designed this regimen to utilize full doses of active agents including docetaxel (T) and H in a novel biweekly schedule to explore efficacy and safety. Methods: Patients (pts) with biopsy proven, clinical stage IIA-IIIC, noninflammatory breast cancer were eligible. HER2+ by FISH was determined locally. CT consisted of epirubicin (E) 100 mg/m2 and cyclophosphamide (C) 600 mg/m2 Q 14 days x 4 followed by T 75 mg/m2 and H 6 mg/kg loading dose, then 4 mg/kg Q 14 days x 4, all with pegfilgrastim support. Surgery was scheduled 20–24 weeks from start after a fifth cycle of H 4mg/kg. EF was measured prior to CT, after EC, after TH and at 6, 12 and 24 months after surgery. Additional adjuvant H to complete 1 year of therapy by conventional schedule was recommended after surgery. The primary endpoint was pCR for invasive cancer in breast and lymph nodes. Results: 30 pts were enrolled at 5 centers: median age was 50.1 (range, 31–72); ethnicity African-American 14, Caucasian 14, other 2; clinical stage IIA, 14, IIB, 4, IIIA, 7, IIIB/C, 5; ER+ 18, PR+ 14; grade 3, 21 and grade 2, 8. Twenty eight pts were evaluable for pathologic response- 2 withdrew before completing treatment, 1 for toxicity. Dose delivery on schedule was >95% for all drugs. Clinical response prior to surgery was cCR 20; cPR 5; and stable 2 pts. Pathologic response: pCR 16 (57%) including 4 with residual DCIS only; 9 pPR, and 2 stable. Mean EF was 63.1 (range, 51–81) before treatment, 62.4 (49–75) after EC and 58.3 (35–74) after TH. Two pts had EF <50% during Neo, one with clinical CHF and 1 additional pt developed CHF during adjuvant single agent H. Both pts had symptomatic improvement with cessation of H. Adverse events were generally mild with 14 grade 3 AEs including 3 episodes of dyspnea and no grade 3 skin toxicity or any grade 4 toxicity noted. Conclusions: Sequential Neo dose-dense Q 14 day EC followed by Q 14 day TH yields a high pCR rate in HER2+ breast cancer with acceptable toxicity profile and no new safety signals noted. No significant financial relationships to disclose.

scholarly journals A Meta-Analysis Study of Polychemotherapy versus Monochemotherapy in Patients of Metastatic Breast Cancer

2016 ◽  
Vol 8 (03) ◽  
Author(s):  
Amal Kumar ◽  
Bhaswat Chakraborty
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Single Agent ◽  
Metastatic Breast ◽  
Nausea And Vomiting ◽  
Tumor Control ◽  
Randomized Controlled Studies ◽  
Significant Difference

Polychemotherapy and intermittent monochemotherapy regimens in metastatic breast cancer were examined in a meta analysis that included both tumor response rate and toxicities. Randomized controlled studies (conducted during 1990-2008) comparing monochemotherapy and poly-chemotherapy in advanced breast cancer patients were selected from electronic databases. Meta-analysis for response rate and toxicities [nausea and vomiting, toxic death, alopecia and reduced white cell count (WCC)] was performed using the MantelHaenszel method. The heterogeneity among the trials was assessed through a χ2 statistic, I2 and visual inspection of the forest plots. Analysis of eligible studies reveals statistical significant difference in response rate (OR 0.72, 95% CI 0.65-0.79), nausea and vomiting (OR 0.80, 95% CI 0.67-0.59), Alopecia (OR 0.75, 95% CI 0.640.88) and reduced WCC (OR 0.55, 95% CI 0.48-0.62) which favours polychemotherapy except toxic death (OR 0.87, 95% CI 0.58-1.29). There was marked evidence of heterogeneity in all end points except toxic death. This meta analysis shows the superiority of efficacy but not of safety of polychemotherapy over that of a single agent. However, the choice of treatment should be based on the response to the therapy, toxicity, patient preference, presence of metastases or imminent complications requiring aggressive and rapid tumor control.

Comparison between gemcitabine-based combination (G) and single-agent chemotherapy (S) for elderly patients (EP) with advanced non-small cell lung cancer (NSCLC): A literature-based meta-analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19586-19586
Author(s):  
I. Carreca ◽  
F. Bellomo ◽  
G. Bronte ◽  
M. Burgio ◽  
A. Carreca ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Meta Analysis ◽  
Single Agent ◽  
Haematological Toxicity ◽  
Phase Iii ◽  
Cochrane Library ◽  
Combination Regimen ◽  
Random Effects Models ◽  
Significant Difference ◽  
Phase Iii Trials

19586 Background: It was estimated that a quarter of all patients who have a diagnosis of NSCLC worldwide are more than 70 years old. This meta-analysis tries to shed light on the controversial results of phase III trials evaluating in NSCLC EP doublets against third generation S. Methods: We performed a literature search using MEDLINE and Cochrane Library. We selected only clinical trials responding to the question of our meta-analysis. Outcomes recorded were 1-year survival rate (1-y SR), overall response rate (ORR) and haematological toxicity (HT). Fixed-effects and random-effects models were used to calculate pooled odds ratios (OR). An OR greater than 1 indicates that doublet is more effective for 1-y SR and ORR and more toxic for HT. Results: Three published randomized controlled phase III trials (SICOG 9909; MILES; AISCAP-SICOG) were selected yielding a total of 1082 patients (G: 426; S: 655) clustered in seven comparisons. Drugs delivered to randomized patients included gemcitabine, vinorelbine and paclitaxel. EP treated with doublets showed respect to control patients a pooled estimate for 1-y SR advantage of 36%, not statistically significant (OR=1.356; 95% CI=0.925–1.990; p>0.05). The pooled estimate for ORR advantage was 57% and statistically significant (OR=1.559; 95% CI=1.220–2.015; p<0.05). However G showed not significant difference for HT (OR=1.168; 95% CI=0.685–1.992; p>0.05). Conclusions: These data confirm in EP superior efficacy and equal tolerability of G in comparison with S previously demonstrated for adult patients. Anyway G seems to not change prognosis of NSCLC EP. It is worthy to note that all the trials analysed showed some biases: early closure of the study, second-line therapy or crossover, lower dosage of drugs in combination regimen, inclusion of unfit or strongly comorbid patients. This meta-analysis doesn’t solve troubles in decision-making of treatment for EP, but suggest to design a better phase III trial including more patients and improving accrual criteria for reducing biases. An indication of a potentially active combination regimen (gemcitabine + paclitaxel) is suggested in SICOG 9909 trial. No significant financial relationships to disclose.

Neoadjuvant single and dual HER2 blockade among patients with localized HER2-positive breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 147-147
Author(s):  
Kerry Lynn Reynolds ◽  
XingXing Cheng ◽  
Ashmeet Bhatia ◽  
Michelle Connolly Specht ◽  
Barbara Lynn Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Grade 3 ◽  
The Impact

147 Background: Dual neoadjuvant HER2 directed therapy is offered only in a clinical trial setting and is not standard of care, but emerging data suggests targeting multiple mechanisms may be more effective. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), and on pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, as well as the impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ breast cancer. Methods: MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and p values were estimated for endpoints using the random effects statistical model. Results: We identified 36 trials (N = 4130). High pCR rates (> 40%) were seen with anthracycline-based chemotherapy and trastuzumab alone, and non-anthracycline based dual HER2 blockade. The addition of trastuzumab to chemotherapy did not improve BCS rate (RR 1.40, p = 0.15), but significantly increased rates of pCR (RR 1.91, p = 0.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, p = 0.84), but significantly increased rates of pCR overall (RR 1.39, p < 0.00001), in both ER+ (RR 1.72, p = 0.01) and ER- subsets (RR 1.91, p = 0.0001), with no increase in grade 3/4 toxicity (RR:1.13, p = 0.16). Dual HER-2 blockade without chemotherapy was associated with pCR in a subset (11.2% - 27%) with minimal toxicity (incidence of grade 3/4 toxicity:1-5%). Higher pCR was associated with improved DFS (RR 2.29, p = 0.006) and OS (RR 4.61, p = 0.009). Conclusions: Neither the addition of trastuzumab to chemotherapy, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS. However,both significantly improve rates of pCR, which is associated with improved DFS and OS. Dual HER2 blockade,with endocrine therapy for ER+, could potentially lessen or even obviate the use of chemotherapy.

scholarly journals Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2− Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-11
Author(s):  
Kai Hong ◽  
Lingli Yao ◽  
Xianneng Sheng ◽  
Dan Ye ◽  
Yu Guo
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Library ◽  
Cyclin Dependent Kinase ◽  
Residual Cancer Burden ◽  
Her2 Breast Cancer

<b><i>Background:</i></b> Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. <b><i>Objective:</i></b> The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2− BC. <b><i>Method:</i></b> We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. <b><i>Results:</i></b> Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 &#x3c; 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81–13.03, <i>p</i> &#x3c; 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39–34.58, <i>p</i> = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17–35.88, <i>p</i> &#x3c; 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04–2.85, <i>p</i> = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59–29.61, <i>p</i> &#x3c; 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40, <i>p</i> = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41–20.11, <i>p</i> &#x3c; 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29–0.87, <i>p</i> = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12–2.07, <i>p</i> = 0.342) and reduce the residual cancer burden (RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, <i>p</i> = 0.121; RCB 2–3: OR = 2.30, 95% CI = 0.89–5.91, <i>p</i> = 0.084). <b><i>Conclusions:</i></b> The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.

Role of anthracyclines in neoadjuvant anti-HER2 regimens for HER2+ breast cancer (BC): A network meta-analysis (NMA).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 577-577
Author(s):  
Giacomo Pelizzari ◽  
Lorenzo Gerratana ◽  
Debora Basile ◽  
Michele Bartoletti ◽  
Camilla Lisanti ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Single Agent ◽  
Credible Interval ◽  
Complete Response ◽  
Current Debate ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
Relevant Role ◽  
Indirect Comparisons

577 Background: It is matter of current debate which would be the best chemotherapy backbone of neoadjuvant HER2-targeted therapy for HER2+ BC. The TRAIN 2 trial showed no significant difference in terms of pathological complete response (pCR) when anthracyclines–based (CTA) or anthracyclines–free regimens (CT) were combined with dual HER2 blockade. However, it remains unclear how anthracyclines may influence the relative benefit across different anti-HER2 treatments. Methods: A systematic review was conducted which included all phase II/III randomized clinical trials (RCTs) comparing different neoadjuvant regimens for HER2+ BC. pCR (yT0/isN0) was the outcome of interest. Indirect comparisons of all combination of anti-HER2 agents with CTA or CT were estimated with a random-effects frequentist NMA. Estimated pCR rates were inferred adopting a Bayesian NMA. Results: 17 RCTs (3933 patients) were included. Overall, 8 arms were identified, comprising all possible combinations of CTA and CT with trastuzumab (H), lapatinib (L) and dual HER2 blockade (D) but also CTA and D only. Odds ratios (OR) for pCR and 95% confidence interval (CI) of selected NMA comparisons are shown in the table. Estimated rates of pCR for each treatment and 95% credible interval (CrI) are reported in the table. Conclusions: Through indirect comparisons, no significant pCR gain was found for CTA vs CT when combined to D, H and L. In particular, considering double vs single-agent anti-HER2 regimens, D-CT remains superior to H-CTA, supporting a possible omission of anthracyclines when dual anti-HER2 block is used. On the contrary, our pooled estimate suggests a more relevant role for anthracyclines when comparing H-CT/A vs CTA. Moreover, we estimated a 4% pCR gain for D-CTA vs D-CT, and an 8% higher pCR rate for H-CTA vs H-CT. [Table: see text]

Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Color Change ◽  
Meta Analysis ◽  
Present Review ◽  
Cochrane Library ◽  
Light Sources ◽  
Eligibility Criteria ◽  
Tooth Color ◽  
Significant Difference ◽  
Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

Copper Concentrations in Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 27 (37) ◽  
pp. 6373-6383 ◽  
Author(s):  
Leila Jouybari ◽  
Faezeh Kiani ◽  
Farhad Islami ◽  
Akram Sanagoo ◽  
Fatemeh Sayehmiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Breast Tissue ◽  
Reference Lists ◽  
Meta Analysis ◽  
Cancer Risks ◽  
Hair Samples ◽  
Significant Difference ◽  
Mean Differences ◽  
Very High

: Breast cancer is the most common neoplasm, comprising 16% of all women's cancers worldwide. Research of Copper (Cu) concentrations in various body specimens have suggested an association between Cu levels and breast cancer risks. This systematic review and meta-analysis summarize the results of published studies and examine this association. We searched the databases PubMed, Scopus, Web of Science, and Google Scholar and the reference lists of relevant publications. The Standardized Mean Differences (SMDs) between Cu levels in cancer cases and controls and corresponding Confidence Intervals (CIs), as well as I2 statistics, were calculated to examine heterogeneity. Following the specimens used in the original studies, the Cu concentrations were examined in three subgroups: serum or plasma, breast tissue, and scalp hair. We identified 1711 relevant studies published from 1984 to 2017. There was no statistically significant difference between breast cancer cases and controls for Cu levels assayed in any studied specimen; the SMD (95% CI) was -0.01 (-1.06 - 1.03; P = 0.98) for blood or serum, 0.51 (-0.70 - 1.73; P = 0.41) for breast tissue, and -0.88 (-3.42 - 1.65; P = 0.50) for hair samples. However, the heterogeneity between studies was very high (P < 0.001) in all subgroups. We did not find evidence for publication bias (P = 0.91). The results of this meta-analysis do not support an association between Cu levels and breast cancer. However, due to high heterogeneity in the results of original studies, this conclusion needs to be confirmed by well-designed prospective studies.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Sign in / Sign up

Export Citation Format

Share Document