Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use* ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics* ; Breast Neoplasms/mortality ; Cytochrome P-450 CYP2D6/genetics* ; Female ; Genotype ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Polymorphism, Single Nucleotide* ; Tamoxifen/therapeutic use*
Keywords
Breast Neoplasms ; Cytochrome p-450 CYP2D6 ; Polymorphism, Single Nucleotide ; Survival Analysis ; Tamoxifen
Abstract
The aim of the study was to evaluate the association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. We evaluated the CYP2D6 genetic polymorphisms in 766 breast cancer patients. Among them, 110 patients whose samples were prospectively collected before surgery and treated with tamoxifen were included to evaluate the association between CYP2D6 and outcomes. The genotypes of CYP2D6 were categorized as extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) according to the activity score. The clinicopathologic features of 110 patients were not significantly different among the three groups except for the T-stage and nodal status. The high T-stage and axillary metastasis were more frequent in the PM group. While recurrence-free and overall survival in the PM group was poorer than the other groups, there was no significant difference between the EM and the IM group. The difference between the PM and the other groups on univariate analysis disappeared on multivariate analysis. These conflicting results suggest that the clinical value of CYP2D6 polymorphisms is still unclear and more large-sized and comprehensively designed trials are necessary.