PMID- 26067721 OWN - NLM STAT- MEDLINE DCOM- 20151230 LR - 20190318 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 13 DP - 2015 Jun 11 TI - Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors: a systematic review and meta-analysis. PG - 139 LID - 10.1186/s12916-015-0373-9 [doi] LID - 139 AB - 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. FAU - Artigalas, Osvaldo AU - Artigalas O AD - Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, UFRGS, Av. Bento Goncalves, 9500 - Predio 43323M CEP: 91501-970 - Caixa Postal 15053, Porto Alegre, Rio Grande do Sul, Brazil. artigalas@gmail.com. AD - Genetics Unit, Children's Hospital, Grupo Hospitalar Conceicao, GHC, Av. Francisco Trein, 596, CEP 91350-200, Porto Alegre, RS, Brazil. artigalas@gmail.com. FAU - Vanni, Tazio AU - Vanni T AD - Coordenacao Geral de Avaliacao de Tecnologias em Saude - CGATS, Department of Science and Technology, Ministry of Health, SCN Quadra 02 Projecao C Subsolo Sala T-004, CEP: 70712-902, Brasilia, DF, Brazil. taziovanni@gmail.com. FAU - Hutz, Mara Helena AU - Hutz MH AD - Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, UFRGS, Av. Bento Goncalves, 9500 - Predio 43323M CEP: 91501-970 - Caixa Postal 15053, Porto Alegre, Rio Grande do Sul, Brazil. mara.hutz@ufrgs.br. FAU - Ashton-Prolla, Patricia AU - Ashton-Prolla P AD - Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, UFRGS, Av. Bento Goncalves, 9500 - Predio 43323M CEP: 91501-970 - Caixa Postal 15053, Porto Alegre, Rio Grande do Sul, Brazil. pprolla@gmail.com. AD - Medical Genetics Service, Hospital de Clinicas de Porto Alegre, HCPA, Rua Ramiro Barcelos, 2350, CEP: 90035-903, Porto Alegre, RS, Brazil. pprolla@gmail.com. FAU - Schwartz, Ida Vanessa AU - Schwartz IV AD - Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, UFRGS, Av. Bento Goncalves, 9500 - Predio 43323M CEP: 91501-970 - Caixa Postal 15053, Porto Alegre, Rio Grande do Sul, Brazil. idadschwartz@gmail.com. AD - Medical Genetics Service, Hospital de Clinicas de Porto Alegre, HCPA, Rua Ramiro Barcelos, 2350, CEP: 90035-903, Porto Alegre, RS, Brazil. idadschwartz@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20150611 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Aromatase Inhibitors) RN - 0 (Biomarkers, Tumor) RN - EC 1.14.14.1 (Aromatase) RN - EC 1.14.14.1 (CYP19A1 protein, human) SB - IM MH - Aromatase/*genetics MH - Aromatase Inhibitors/*pharmacology MH - Biomarkers, Tumor/genetics MH - *Breast Neoplasms/diagnosis/drug therapy/genetics MH - Drug Resistance, Neoplasm/*genetics MH - Drug-Related Side Effects and Adverse Reactions/*genetics MH - Female MH - Genetic Testing MH - Haplotypes MH - Humans MH - Pharmacogenetics MH - Polymorphism, Single Nucleotide MH - Predictive Value of Tests MH - Prognosis PMC - PMC4475294 EDAT- 2015/06/13 06:00 MHDA- 2015/12/31 06:00 PMCR- 2015/06/11 CRDT- 2015/06/13 06:00 PHST- 2015/01/17 00:00 [received] PHST- 2015/05/18 00:00 [accepted] PHST- 2015/06/13 06:00 [entrez] PHST- 2015/06/13 06:00 [pubmed] PHST- 2015/12/31 06:00 [medline] PHST- 2015/06/11 00:00 [pmc-release] AID - 10.1186/s12916-015-0373-9 [pii] AID - 373 [pii] AID - 10.1186/s12916-015-0373-9 [doi] PST - epublish SO - BMC Med. 2015 Jun 11;13:139. doi: 10.1186/s12916-015-0373-9.