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Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis.

ABSTRACT: 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.

SUBMITTER: Artigalas O

PROVIDER: S-EPMC4475294 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis.

Artigalás Osvaldo O Vanni Tazio T Hutz Mara Helena MH Ashton-Prolla Patricia P Schwartz Ida Vanessa IV

BMC medicine 20150611

<h4>Background</h4>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.<h4>Methods</h4>A systematic review was performed in MEDLINE, EMBAS ...[more]

PMID: 26067721

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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:ObjectiveTo evaluate the effects of Physical Therapies (PTs) on improvement in psychosomatic symptoms and quality of life (QOL) in breast cancer patients.Data sourcesSeven databases (MEDLINE, EMBASE, Cochrane CENTRAL, China National Knowledge Infrastructure, Wangfang, VIP, and China Biology Medicine disc databases) were systematically searched from the database inception through May 18, 2021.Study selectionRandomized controlled trials (RCTs) which compared acupuncture or exercise with a sham control or usual care for the treatment of aromatase inhibitors (AIs)-related psychosomatic symptoms and QOL.Data extraction and synthesisData were screened and extracted independently using predesigned forms. The quality of RCTs was assessed with the Cochrane Handbook for Systematic Reviews of Interventions. The effect size was calculated via random-effects modeling. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach.Main outcomes and measuresThe score of pain was measured with BPI scale and Western Ontario and the McMaster Universities Index (WOMAC) scale. Emotional state was measured with Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS-A), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The QOL score was measured by self-reported measurements, including the Functional Assessment of Cancer Therapy-General (FACT-G) scale and 36-Item Short Form Survey (SF-36) scale.ResultsEleven RCTs (with 830 patients) were included in the systematic review, and data from 10 RCTs (with 798 patients) were used in the meta-analysis. Results showed acupuncture significantly reduced worst pain scores (P < 0.00001, I 2 = 83.5%) [SMD = -0.81, 95% CI (-1.51, -0.11)], but the effect of exercise therapies was not significant in overall change in worst pain scores (P =0.006, I 2 = 72.3%) [SMD = -0.30, 95% CI (-0.76, 0.16)]. Both acupuncture and exercise resulted in little to no difference in overall change in HADS-A subscale (P = 0.026<0.05, I 2 = 79.8%) [WMD = -0.21, 95% CI (-3.44, 3.03)], PSQI subscale (P = 0.488, I 2 = 0%) [WMD = 0.98, 95% CI (-0.57, 2.53)], and FACIT-Fatigue subscale (P = 0.022<0.05, I 2 = 81.0%) [WMD = 1.6, 95% CI (-5.75, 8.94)]. Exercise (compared with usual care) was associated with improving overall change in health-related QOL (subscales of SF-36 tool) (P = 0, I 2 = 72.1%) [WMD = 7.97, 95% CI (5.68, 10.25)] and cancer-specific QOL (subscales of FACT-G tool) (P = 0.304, I 2 = 16%) [WMD = 1.16, 95% CI (0.34, 1.97)].Conclusions and relevanceThis systematic review and meta-analysis suggested that based on moderate-level evidence, acupuncture was associated with significant reductions in pain intensity, and exercise might improve QOL in breast cancer patients treated with AIs. However, in psychosomatic symptoms such as anxiety, sleep disturbance, and fatigue, acupuncture and exercise training did not result in significant improvements.

Dataset Information

Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis.

Publications

Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis.

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