Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen  

作　　者：Christos Markopoulos Stylianos Kykalos Dimitrios Mantas 

机构地区：[1]Breast Unit, 2nd Propedeutic Department of Surgery, Faculty ofMedicine,National and Kapodistrian University of Athens

出　　处：《World Journal of Clinical Oncology》2014年第3期374-381,共8页世界临床肿瘤学杂志（英文版）

摘　　要：Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450(CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning(null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, par-ticularly in terms of response to tamoxifen therapy and breast cancer outcome.Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450(CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning(null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, par-ticularly in terms of response to tamoxifen therapy and breast cancer outcome.

关 键 词：CYP2D6 TAMOXIFEN BREAST CANCER ADJUVANT treatment 

分 类 号：R737.9[医药卫生—肿瘤]