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) 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.
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.