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World J Clin Oncol. Aug 10, 2014; 5(3): 374-381
Published online Aug 10, 2014. doi: 10.5306/wjco.v5.i3.374
Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen
Christos Markopoulos, Stylianos Kykalos, Dimitrios Mantas
Christos Markopoulos, Stylianos Kykalos, Dimitrios Mantas, Breast Unit, 2nd Propedeutic Department of Surgery, Faculty of Medicine, National and Kapodistrian University of Athens, 11521 Athens, Greece
Author contributions: All contributed equally to this work; Markopoulos C designed the research and edited the final version of the manuscript; Kykalos S and Mantas D prepared the draft of the manuscript.
Correspondence to: Christos Markopoulos, MD, Professor of Surgery, Breast Unit, 2nd Propedeutic Department of Surgery, Faculty of Medicine, National and Kapodistrian University of Athens, 8, Iassiou street, 11521 Athens, Greece. cmarkop@hol.gr
Telephone: +30-210-7221413 Fax: +30-210-7247168
Received: December 27, 2013
Revised: March 10, 2010
Accepted: May 31, 2014
Published online: August 10, 2014
Processing time: 216 Days and 22.6 Hours
Abstract

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, particularly in terms of response to tamoxifen therapy and breast cancer outcome.

Keywords: CYP2D6; Tamoxifen; Breast cancer; Adjuvant treatment

Core tip: Currently, routine cytochrome P450 (CYP)2D6 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, particularly in terms of response to tamoxifen therapy and breast cancer outcome.