Prospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2022; 13(8): 712-724
Published online Aug 24, 2022. doi: 10.5306/wjco.v13.i8.712
Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer
Ern-Yu Tan, Lavina Bharwani, Yee-Hong Chia, Richie C T Soong, Sherylyn S Y Lee, Juliana J C Chen, Patrick M Y Chan
Ern-Yu Tan, Sherylyn S Y Lee, Juliana J C Chen, Patrick M Y Chan, Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
Ern-Yu Tan, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
Ern-Yu Tan, Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore
Lavina Bharwani, Yee-Hong Chia, Department of Medical Oncology, Tan Tock Seng Hospital, Singapore 308433, Singapore
Richie C T Soong, Cancer Science Institute of Singapore, National University of Singapore, Singapore 119077, Singapore
Author contributions: Tan EY designed and performed the research study, analyzed the data and wrote the manuscript; Bharwani L and Chia YH performed study procedures in the protocol; Soong RCT was responsible for CYP2D6 genotype and verification of the phenotype; Lee SSY, Chen JJC and Chan PMY contributed to data collection, data analyses and review of the manuscript; All authors have read and approved the final manuscript.
Supported by the NHG-KTPH Small Innovative Grants (SIG), No. SIG/11009 and No. SIG/15025.
Institutional review board statement: This study has obtained Ethics Committee approval (2011/00017).
Clinical trial registration statement: This study is registered at the Health Sciences Authority (Application No. 1140684B).
Informed consent statement: Documented consent was obtained from all patients recruited into this study for the use of blood samples and genomic and clinical data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ern-Yu Tan, DPhil, FRCS (Gen Surg), MBBS, Associate Professor, Department of General Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
Received: April 7, 2021
Peer-review started: April 7, 2021
First decision: June 28, 2021
Revised: August 8, 2021
Accepted: July 18, 2022
Article in press: July 18, 2022
Published online: August 24, 2022

There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P450 2D6 (CYP2D6) polymor-phisms.


To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.


Eighty-two women were recruited. Seventy-eight completed CYP2D6 genotyping and were categorized into poor, intermediate (IM) and extensive or ultra metabolizer phenotypes. Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.


More than 70% of the women had an IM phenotype, 32% an extensive or ultra metabolizer phenotype, and 0% had a poor metabolizer phenotype. Regardless of genotype, more women opted for aromatase inhibitors. Overall, 80% of women completed 5 years of hormonal therapy. Five women developed recurrence, 3 contralateral breast cancer, 5 died, and 1 was diagnosed with a second primary cancer. Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype, though not statistically significant [P = 0.743, hazard ratio (HR): 1.441, 95% confidence interval (CI): 0.191 to 10.17 and P = 0.798, HR: 1.327, 95%CI: 0.172 to 9.915, respectively]. Women receiving aromatase inhibitors also appeared to have a better, but also nonsignificant, 5-year recurrence-free and overall survival (P = 0.253, HR: 0.368, 95%CI: 0.031 to 0.258 and P = 0.292, HR: 0.252, 95%CI: 0.005 to 4.951, respectively).


The IM phenotype was highly prevalent but was not associated with clinical outcome.

Keywords: Functional cytochrome P450 2D6 polymorphisms, Breast cancer, Hormonal therapy

Core Tip: We studied the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in guiding the selection of hormonal agents in women with hormone-responsive breast cancer. The CYP2D6 intermediate metabolizer phenotype was highly prevalent in our women, while the poor metabolizer phenotype was rare. We did not observe any significant association between the CYP2D6 phenotypes and recurrence-free or overall survival in our study, although it could be because most women opted for aromatase inhibitors regardless of CYP2D6 phenotype. There was a non-significant trend towards better survival associated with aromatase inhibitor use over tamoxifen.