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Effect of chemotherapy and aromatase inhibitors in the adjuvant treatment of breast cancer on glucose and insulin metabolism-A systematic review.

ABSTRACT: INTRODUCTION:Breast cancer (BC) is the most common cancer among women worldwide. With increasing survival rates, focus has expanded to long-term adverse effects of adjuvant chemotherapy and/or aromatase inhibitors. Weight gain during chemotherapy has been well documented, but the underlying mechanisms remain unclear. A change in glucose and insulin metabolism is a possible consequence. METHODS:We searched PubMed on the 4th of May 2018, and found eight articles that compared measurements of glucose and insulin before and after chemotherapy and/or aromatase inhibitors in woman with BC. RESULTS:A general trend of increased glucose and insulin is seen and likely to be caused by weight gain and/or changes in body composition as a consequence of adjuvant treatment of BC. DISCUSSION:Due to methodological limitations including short follow-up times and small sample sizes, further studies are required to better describe metabolic consequences of adjuvant chemotherapy and/or aromatase inhibitors. Future studies could help identify patients in high-risk of developing cardiometabolic disease after BC treatment.

SUBMITTER: Buch K

PROVIDER: S-EPMC6346263 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Effect of chemotherapy and aromatase inhibitors in the adjuvant treatment of breast cancer on glucose and insulin metabolism-A systematic review.

Buch Kristian K Gunmalm Victoria V Andersson Michael M Schwarz Peter P Brøns Charlotte C

Cancer medicine 20181218 1

<h4>Introduction</h4>Breast cancer (BC) is the most common cancer among women worldwide. With increasing survival rates, focus has expanded to long-term adverse effects of adjuvant chemotherapy and/or aromatase inhibitors. Weight gain during chemotherapy has been well documented, but the underlying mechanisms remain unclear. A change in glucose and insulin metabolism is a possible consequence.<h4>Methods</h4>We searched PubMed on the 4th of May 2018, and found eight articles that compared measur ...[more]

PMID: 30561133

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Project description:BackgroundCardiovascular events (CVEs) was considered as one of the primary cause to reduce the quality of life in breast cancer patients with aromatase inhibitors (AIs) treatment, which has not been sufficiently addressed. The aim of this study was to assess the correlation between risk of CVEs and AIs in patients with breast cancer.MethodsIncluded studies were obtained from the databases of Embase, Pubmed, Cochrane Library, Clinical Trials.gov, and reference lists. The main outcome measures were overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Furthermore, the association and the risk differences among different tumor types, AIs,ages,or treatment regimens were conducted. Fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. Our analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsSeventeen studies, which included 44,411 subjects, were included in our analyses. The overall incidence of CVEs in AIs group was 13.02% (95% CI: 8.15-20.17%) and almost all of the high-grade CVEs occurred in patients treated with AIs. The pooled ORs of CVEs was 0.9940 (95% CI: 0.8545-1.1562). Under sub-group analysis, the incidence of CVEs related to exemestane was higher than that of controls (OR = 1.1564, 95% CI: 1.0656-1.2549), but no statistical differences in risk of CVEs were found in other sub-group analysis. No evidence of publication bias was found for incidence of CVEs in our meta-analysis by a funnel plot.ConclusionsThese results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls, and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs. Further studies are recommended to investigate this association and the risk differences among different tumor types, AIs or treatment regimens.

Project description:BACKGROUND:Many clinical trials have shown the efficacy of aromatase inhibitors (AIs) in the management of breast cancer (BC). There is growing evidence that CYP19A1 single-nucleotide polymorphisms (SNPs) are associated with clinical response (CR) and adverse effects (AEs) among BC patients treated with AIs. The aim of this study was to analyze the association between CYP19A1 polymorphisms and AI treatment in BC patients. METHODS:A systematic review was performed in MEDLINE, EMBASE, and LILACS. A meta-analysis was conducted to compare the association between CYP19A1 variants and treatment response among BC patients. RESULTS:A total of 12 studies were included in the final analysis. There was significant variation among the populations studied and the SNPs and outcomes investigated. A meta-analysis was only possible for the evaluation of SNP rs4646 vs. the wild-type variant with respect to time to progression (TTP) among metastatic BC patients treated with AI. TTP was significantly increased in patients with the rs4646 variant compared with the wild-type gene (hazard ratio (HR) = 0.51 [95 % confidence interval (CI), 0.33-0.78], P = 0.002). Seven studies analyzed the association between AEs with different polymorphisms of CYP19A1. Although there was a statistically significant association with musculoskeletal adverse events (rs934635, rs60271534, rs700518rs, and haplotype M_3_5) and with vasomotor symptoms (rs934635, rs1694189, rs7176005, and haplotype M_5_3) in individual studies, similar associations were not observed in further studies. No statistically significant association between musculoskeletal AEs and SNPs rs4646, rs10046, rs727479, and rs1062033 was found. CONCLUSIONS:These findings suggest that the presence of the rs4646 variant may be a predictive factor of the benefit of AI treatment for BC. The effects of CYP19A1 polymorphisms on clinical outcomes were most often detected in individual studies, suggesting that longer-term studies will better clarify these associations. Additional studies are needed to clarify the predictive value of other SNPs and whether CYP19A1 genotyping should be used to guide AI treatment.

Project description:Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we performed a network meta-analysis to identify the most effective adjuvant chemotherapy regimen.To find the most effective adjuvant therapy regimen for early-stage breast cancer.We searched MEDLINE, Embase, and the Cochrane Library for articles published before June 2015; the American Society of Clinical Oncology annual meeting abstracts from January 1983 through December 2014; and the American Association for Cancer Research annual meeting abstracts from January 1916 through December 2014. Additionally, we manually searched bibliographies for related references.We included randomized clinical trials of adjuvant treatments for early-stage breast cancer that compared 2 or more of the following: no adjuvant chemotherapy; sequential anthracycline-cyclophosphamide and taxane (AC-T); concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens.We followed the PRISMA guidelines. Two investigators independently selected the articles and extracted information. Disagreements were resolved by discussion with another author. Quality was assessed by Cochrane risk-of-bias method. Data were pooled using random-effects models.We used network meta-analysis to test the most effective adjuvant therapy regimen in terms of overall survival (OS) by comparing regimens listed in the National Comprehensive Cancer Network guidelines and platinum-containing regimens.We identified 24 trials. The TC and platinum-containing regimens had OS benefit similar to that of sequential AC-T (TC hazard ratio [HR], 0.93; 95% CI, 0.62-1.40; and platinum HR, 0.93; 95% CI, 0.66-1.31). Patients treated with CMF or AC had significantly worse OS than those treated with sequential AC-T (CMF HR, 1.56; 95% CI, 1.32-1.85; and AC HR, 1.22; 95% CI, 1.10-1.37). Platinum-containing regimens tended to be more toxic than sequential AC-T. The toxicity of TC was similar to or less than that of sequential AC-T. Meta-regression analysis showed that hormone receptor status did not impact the HRs for OS for any regimen.Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.

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Effect of chemotherapy and aromatase inhibitors in the adjuvant treatment of breast cancer on glucose and insulin metabolism-A systematic review.

Publications

Effect of chemotherapy and aromatase inhibitors in the adjuvant treatment of breast cancer on glucose and insulin metabolism-A systematic review.

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