by Isabel Blancas,
Marina Linares-Rodríguez, Eduardo Martínez de Dueñas, Carmen Herrero-Vicent,
María D. Molero-Mir, José M. Garrido, Fernando Rodríguez-Serrano
The Breast: Published: March 23, 2023
Purpose
Tamoxifen is a drug
used for hormone receptor-positive breast cancers, primarily metabolised by the
CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays
varying degrees of activity depending on its genotype. This study aims to
analyse the effect of an early increase in tamoxifen dose in poor metabolisers
(PM) on survival.
Methods
We enrolled 220
patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6
polymorphisms were determined, and the phenotype was estimated according to the
Clinical Pharmacogenetics Implementation Consortium. Disease-free survival
(DFS) and overall survival (OS) were analysed considering the entire patient
group, and a subgroup of 110 patients selected by Propensity Score Matching
(PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except
PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4
months and 60 mg/day for 4 months before returning to the standard dose of 20
mg/day until completing 5 years of treatment.
Results
The analysis of the
influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup
revealed no significant differences for DFS or OS. Furthermore, DFS and OS were
analysed in relation to various covariates such as age, histological grade,
nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only
age, histological grade, nodal status, and chemotherapy treatment demonstrated
statistical significance.
Conclusion
An early increase
in tamoxifen dose in PM patients is not associated with survival differences
among CYP2D6 phenotypes.
