Meta-analysis of side effects (SEs) of aromatase inhibitors (AI) and of tamoxifen (TAM) in large randomized clinical trials (RCT)

11015 Background: The published data from large RCTs for the endocrine adjuvant treatment of postmenopausal breast cancer patients (ATAC and BIG 1–98) have shown us the difference in SEs between an AI vs TAM. Observed SEs in these trials are the result of an effect of both drugs: e.g. AIs induce bone loss and lead to an increase in fracture risk whereas TAM reduces fracture risk. We did a meta- analysis of comparable SEs in ATAC and BIG and combined this information with a second meta-analysis comparing an AI vs nil and a third meta-analysis comparing TAM vs nil. Methods: A relative risk (RR) meta-analysis was done on published data of SEs comparing AI vs TAM (ATAC Lancet 2002; BIG 1–98 NEJM 2005). SEs studied were: (1) fracture risk; (2) ischemic cerebrovascular events; (3) hypercholesterolemia; (4) hot flushes; (5) venous thromboembolic events and (6) any musculoskeletal events. Data for the comparison of AI vs nil were taken from MA.17 (NEJM 2003) and the combined arm of ATAC (Lancet 2002). Data for the comparison of TAM vs nil were taken from the P1 (JNCI 1998) and IBIS 1 (Lancet 2002). The assumption of a fixed effects model was used unless significant heterogeneity (Cochran Q test) was found. Results: In the comparison of fractures (ATAC and BIG combined) there was a 50% increase in RR for fractures in the AI arm. Our second meta-analysis showed that half of this increase was due to an effect of the AI and (according to the third meta- analysis) about half was due to a decrease of the RR for fractures thanks to TAM. Significant differences in cerebrovascular, hypercholesterolemia and hot flushes related events were due to a TAM effect. Concerning musculoskeletal events, significant heterogeneity was found when comparing the effect of an AI in the presence or absence of TAM. When patients get TAM together with an AI (ATAC combined arm) there is no increase in musculoskeletal events compared to the TAM alone arm. When an AI was compared to nil (MA.17) a significant increase in events was observed. We hypothesize that this heterogeneity is due to an estrogenic effect of TAM. Conclusion: This RR analysis allowed us to dissect the SEs profile of an AI and of TAM. The results for musculoskeletal events generate a new biological hypothesis. No significant financial relationships to disclose.

Download Full-text

Efficacy of Low-Dose Paroxetine for the Treatment of Hot Flushes in Surgical and Physiological Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Trials

Medicina ◽

10.3390/medicina55090554 ◽

2019 ◽

Vol 55 (9) ◽

pp. 554

Author(s):

Gaetano Riemma ◽

Antonio Schiattarella ◽

Marco La Verde ◽

Giuseppina Zarobbi ◽

Simone Garzon ◽

...

Keyword(s):

Clinical Trials ◽

Postmenopausal Women ◽

Sleep Disturbances ◽

Low Dose ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Hormonal Treatment ◽

Significant Heterogeneity ◽

Hot Flushes ◽

Night Time

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) −7.97 [−10.51, −5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, −0.40 awakenings/night [−1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.

Download Full-text

The relationship between time to surgery(TTS) after neoadjuvant chemotherapy (NAC)and survival in breast cancer patients: meta-analysis

10.21203/rs.3.rs-44882/v1 ◽

2020 ◽

Author(s):

YongCheng Su ◽

XiaoGang Zheng

Keyword(s):

Neoadjuvant Chemotherapy ◽

Random Effects ◽

Fixed Effects ◽

Meta Analysis ◽

Disease Free Survival ◽

Significant Heterogeneity ◽

Breast Cancer Patients ◽

Free Survival ◽

The Impact ◽

The Relationship

Abstract PURPOSE: This meta-analysis aims to evaluate the impact of delaying surgery in operable breast tumor patients after neoadjuvant chemotherapy (NAC) on survival.METHODS: An electronic literature retrieval was conducted on PubMed/Medline and EMBASE((between January 2000 and June 2020).The primary end point was overall survival(OS),secondary end points included disease-free survival (DFS) or recurrence-free survival (RFS).The HR with 95% confidence intervals were calculated using a random-effects or fixed-effects model.RESULTS: The combined HR for OS was 1.52(95% CI 1.29-1.78; P = 0.000) by fixed-effects model.No statistically significant heterogeneity was found (P=0.114;I2=39.8%).The pooled HR for RFS/DFS was 1.47 (95%CI: 1.27- 1.71,I2=61.9%) by random-effects model, with significant heterogeneity.CONCLUSION: Our meta-analysis revealed a significant adverse association between longer TTS after NAC and more inferior OS and RFS/DFS in patients with breast cancer.Clinicians and patients should minimize surgical delay after NAC as much as possible.

Download Full-text

Use of Statins and Breast Cancer: A Meta-Analysis of Seven Randomized Clinical Trials and Nine Observational Studies

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.7045 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8606-8612 ◽

Cited By ~ 139

Author(s):

Stefanos Bonovas ◽

Kalitsa Filioussi ◽

Nikolaos Tsavaris ◽

Nikolaos M. Sitaras

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Publication Bias ◽

Observational Studies ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Fixed Effects Model

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.

Download Full-text

Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Journal of Oncology ◽

10.1155/2018/6279871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Sunil Badami ◽

Sunil Upadhaya ◽

Ravi Kanth Velagapudi ◽

Pushyami Mikkilineni ◽

Ranju Kunwor ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Random Effect ◽

Eastern Cooperative Oncology Group ◽

Advanced Melanoma ◽

Cochrane Library ◽

Molecular Characteristics ◽

Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

Download Full-text

The impact of lifestyle interventions on therapy associated side effects in postmenopausal breast cancer survivors: systematic reviews and meta-analysis

10.21203/rs.2.18906/v1 ◽

2019 ◽

Author(s):

Jean Paul Muambngu Milambo ◽

Maritha Kotze ◽

John Akudugu

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Breast Cancer Survivors ◽

Meta Analysis ◽

Postmenopausal Breast Cancer ◽

Controlled Trials ◽

Lifestyle Interventions ◽

Breast Cancer Patients ◽

Related Quality

Abstract Background: Medically Supervised Exercise (MSE) are advisable for the prevention and treatment related side effects among breast cancer survivors. Aerobic and resistance either exercise, separately or in combination, have been shown to improve physical functioning and manage some symptoms in breast cancer patients. However, the level of evidence on the effects of lifestyle interventions on therapy related adverse events and the required dose responses of exercises are not yet systematically reviewed. This review was conducted to assess the efficacy of medically supervised exercises(MSE) coupled with diet in preventing/managing aromatase inhibitors induced adverse events and improving range of motion(ROM) and heath related quality of life (HRQOL) in postmenopausal breast cancer patients following treatment. Methods: Two independent authors extracted data using PRISMA guidelines of published clinical trials. We searched the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, as well as clinical practice guidelines. We included only randomized controlled trials that examined exercise interventions coupled with diet interventions in postmenopausal breast cancer women. Health related quality of life (HRQOL) and range of motion were assessed as the main outcomes. Results: Random effects meta-analysis was conducted for pooling of the effect size. The age of patients varied from 50 to 60 years. The results illustrate that the mean difference (MD) in improving ROM in the MSE group versus no supervised exercises was 1.35% (95% CI: 0.63 to 2.07%, P = 0.0002; heterogeneity: Tau² = 0.71; Chi² = 112.14, df = 5 (P < 0.00001); I² = 96%). A summary of the data shows that supervised exercises significantly improved ROM and HRQOL in postmenopausal BCS on endocrine therapy compared to no supervised exercises 3.02 (95% CI: 2.59 to 3.45, P < 0.00001). These outcomes show that lifestyle interventions (MSE +diet) have positive effects on AI-associated adverse events and likely improve ROM and HRQOL in postmenopausal BC patients. Conclusion: The evidence was based on a body of research with moderate study quality. Moreover, further studies are recommended to assess the effect of lifestyle interventions on markers of inflammation as the predictors of treatment non-response and associated comorbidities.

Download Full-text

Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies

Integrative Cancer Therapies ◽

10.1177/1534735417712007 ◽

2017 ◽

Vol 17 (2) ◽

pp. 217-225 ◽

Cited By ~ 20

Author(s):

Kejia Hu ◽

David Frederick Callen ◽

Jiayuan Li ◽

Hong Zheng

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Overall Survival ◽

Cancer Patients ◽

Dose Response ◽

Fixed Effects ◽

Meta Analysis ◽

Breast Cancer Patients ◽

Fixed Effects Model ◽

Vitamin D Levels

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.

Download Full-text

Prognostic Role of miR-221 and miR-222 Expression in Cancer Patients: A Systematic Review and Meta-Analysis

Cancers ◽

10.3390/cancers11070970 ◽

2019 ◽

Vol 11 (7) ◽

pp. 970 ◽

Cited By ~ 5

Author(s):

Gloria Ravegnini ◽

Sarah Cargnin ◽

Giulia Sammarini ◽

Federica Zanotti ◽

Justo Lorenzo Bermejo ◽

...

Keyword(s):

Systematic Review ◽

Cancer Patients ◽

Meta Analysis ◽

Fine Tuning ◽

High Expression ◽

Cochrane Library ◽

Published Data ◽

Significant Heterogeneity ◽

Free Survival

Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.

Download Full-text

Music Therapy in Pain and Anxiety Management during Labor: A Systematic Review and Meta-Analysis

Medicina ◽

10.3390/medicina56100526 ◽

2020 ◽

Vol 56 (10) ◽

pp. 526

Author(s):

Rocio Santiváñez-Acosta ◽

Elena de las Nieves Tapia-López ◽

Marilina Santero

Keyword(s):

Music Therapy ◽

Pain Intensity ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Final Analysis ◽

Beneficial Effects ◽

Quasi Experimental ◽

Vas Scores ◽

Mean Differences

Background and Objective: The study of music therapy in labor is unknown. The main objective of this research was to evaluate the effectiveness of music therapy to manage pain and anxiety during labor. Materials and Methods: A search strategy was used with PubMed/MEDLINE, LILACS, Cochrane, TRIPDATABASE, and Google Scholar. The selection criteria were based on randomized clinical trials; quasi-experimental research on pain intensity and anxiety during labor was evaluated. The primary outcomes were measured by the Visual Analogue Scale (VAS). A meta-analysis of the fixed effects was performed using mean differences (MD). Twelve studies were included for the final analysis, six (778 women) of which were meta-analyzed. Results: Decreased VAS scores for pain intensity associated with music therapy were found in the latent (MD: −0.73; 95% CI −0.99; −0.48) and active (MD: −0.68; 95% CI −0.92; –0.44) phases of labor. VAS scores for anxiety decreased both in the latent (MD: −0.74; 95% CI −1.00; −0.48) and active (MD: −0.76; 95% CI −0.88; −0.64) phases. Conclusion: Music therapy seems to have beneficial effects on pain intensity and anxiety during labor, especially for women giving birth for the first time. However, the evidence is qualified as low.

Download Full-text

Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600819898696 ◽

2020 ◽

Vol 35 (1) ◽

pp. 57-64

Author(s):

Jiajie Fang ◽

Xuanli Xu ◽

Qiqi Mao ◽

Yufan Ying ◽

Xu Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Fixed Effects ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Healthy Controls ◽

Fixed Effects Model ◽

Increased Risk ◽

Carcinoma Risk

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk. Methods: Observational studies that evaluated the association between circulating adiponectin and renal cell carcinoma risk were identified via a systematic search of PubMed and Embase databases. The difference between circulating adiponectin in renal cell carcinoma cases and healthy controls, and the multivariable adjusted association between circulating adiponectin and renal cell carcinoma risk were evaluated. A random effects model was used if significant heterogeneity existed; otherwise a fixed effects model was applied. Results: Eight case-control studies with 2624 renal cell carcinoma cases and 2904 healthy controls were included. Pooled results showed that circulating adiponectin was significantly lower in renal cell carcinoma cases than in healthy controls (mean difference = −1.08 ug/mL; 95% confidence interval (CI) −1.62, −0.54; P < 0.001). Higher circulating adiponectin was independently associated with a significantly lowered risk of renal cell carcinoma (adjusted odds ratio for 1 SD increment of adiponectin = 0.78; 95% CI: 0.63, 0.96; P = 0.02). Subgroup analyses according to characteristics including study design, ethnics of participants, blood samples, numbers of participants, mean ages of participants, and study quality showed consistent results. Conclusions: Lower circulating adiponectin is associated with increased risk of renal cell carcinoma. The potential pathophysiological mechanisms underlying the role of circulating adiponectin in the pathogenesis of renal cell carcinoma deserve further investigation.

Download Full-text