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
Research background

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

Research motivation

Tamoxifen is still the first-line agent for premenopausal women and for those with intolerable AI-related side effects. It is therefore necessary to verify the effectiveness of tamoxifen in view of the high prevalence of reduced function CYP2D6 polymorphisms in Asians.

Research objectives

We evaluated the frequency of CYP2D6 polymorphisms and its association with clinical outcome. We also evaluated treatment-related side effects in order to better determine the risk:benefit ratio.

Research methods

We designed a single-arm prospective study to evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.

Research results

More than 70% of the women in our study had an intermediate metabolizer phenotype. Regardless of genotype, more women opted for aromatase inhibitors. Women with the extensive or ultra metabolizer phenotype had slightly better but nonsignificant 5-year recurrence-free and overall survival compared to women with the intermediate metabolizer phenotype. Women on AIs appeared to have better but also nonsignificant 5-year recurrence-free and overall survival.

Research conclusions

The intermediate metabolizer phenotype was highly prevalent in our local women but was not associated with clinical outcome.

Research perspectives

Data on the effect of CYP2D6 polymorphisms on tamoxifen efficacy remains conflicting. More studies in Asian women would help to clarify this association.