Published online Aug 24, 2022. doi: 10.5306/wjco.v13.i8.712
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) polymorphisms.
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.
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.
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.
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.
The intermediate metabolizer phenotype was highly prevalent in our local women but was not associated with clinical outcome.
Data on the effect of CYP2D6 polymorphisms on tamoxifen efficacy remains conflicting. More studies in Asian women would help to clarify this association.