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CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(12): 794-799
DOI: 10.1055/s-0038-1676303
Review Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer

Impactos do polimorfismo genético do citocromo P450 2D6 (CYP2D6) na terapia com tamoxifeno para câncer de mama
Lucas Soares Bezerra
1   Epidemiology and Cardiology Research Group, Department of Health Sciences, Universidade Federal de Pernambuco, Recife, PE, Brazil
2   School of Medicine, Department of Health Sciences, Faculdade Mauricio de Nassau, Cabo de Santo Agostinho, Recife, PE, Brazil
,
Marcelo Antônio Oliveira Santos-Veloso
1   Epidemiology and Cardiology Research Group, Department of Health Sciences, Universidade Federal de Pernambuco, Recife, PE, Brazil
2   School of Medicine, Department of Health Sciences, Faculdade Mauricio de Nassau, Cabo de Santo Agostinho, Recife, PE, Brazil
,
Natanael da Silva Bezerra Junior
1   Epidemiology and Cardiology Research Group, Department of Health Sciences, Universidade Federal de Pernambuco, Recife, PE, Brazil
,
Lucilia Carvalho da Fonseca
2   School of Medicine, Department of Health Sciences, Faculdade Mauricio de Nassau, Cabo de Santo Agostinho, Recife, PE, Brazil
3   Department of Gynecology and Obstetrics, Universidade de São Paulo, São Paulo, SP, Brazil
,
Wivianne Lisley Andrade Sales
2   School of Medicine, Department of Health Sciences, Faculdade Mauricio de Nassau, Cabo de Santo Agostinho, Recife, PE, Brazil
› Author Affiliations
Further Information

Publication History

10 June 2018

22 October 2018

Publication Date:
07 December 2018 (online)

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Abstract

Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMX is the development of drug resistance caused by molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of CYP2D6 polymorphisms and how they can affect the results of TMX in breast cancer treatment. The keywords CYP2D6, tamoxifen, and breast cancer were searched in the PubMed, Scopus, The Cochrane Library, Scielo, and Bireme databases. Studies related to other types of neoplasms or based on other isoenzymes from cytochrome P450, but not on CYP2D6, were excluded. The impact of CYP2D6 polymorphisms in the TMX resistance mechanism remains unclear. The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease.

Resumo

O tamoxifeno é a principal droga que pode ser utilizada como tratamento hormonal adjuvante em pacientes portadoras de câncer de mama receptor hormonal positivo tanto na pré- quanto na pós-menopausa. Uma das maiores barreiras em seu uso é o desenvolvimento de resistência medicamentosa causada por meio de processos moleculares relacionados a mecanismos genéticos e epigenéticos, como a ação dos polimorfismos do gene citocromo P450 2D6 (CYP2D6) e seus metabólitos. O presente estudo busca revisar as descobertas recentes acerca dos impactos dos polimorfismos do gene CYP2D6 e de como eles podem afetar os resultados do tamoxifeno na terapêutica do câncer de mama. As palavras-chave CYP2D6, tamoxifeno e câncer de mama foram buscadas nas bases de dados Pubmed, Scopus, The Cochrane Library, Scielo e Bireme. Estudos relacionados com outros tipos de câncer ou relacionados a outras isoenzimas do citocromo P450 que não o CYP2D6 foram excluídos. O impacto do polimorfismo do CYP2D6 nos mecanismos de resistência ao tamoxifeno permanecem controversos. O gene CYP2D6 parece reduzir a eficácia do TMX; entretanto, os principais fatores associados a falha terapêutica são morbimortalidade e a progressão da doença

Keywords

cytochrome P-450 CYP2D6 - polymorphism genetic - tamoxifen - breast neoplasms - therapeutic uses

Palavras-chave

citocromo P-450 CYP2D6 - polimorfismo genético - tamoxifeno - neoplasias da mama - usos terapêuticos
 

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