Charoenchokthavee W, et al. – The effects of CYP2D6 and CYP3A5 polymorphisms on the levels of tamoxifen (TAM) were analysed. In addition, researchers planned to determine its metabolites in the plasma of breast cancer patients. Via N–desmethyl tamoxifen (NDMT) subpathway, CYP2D6 polymorphisms appeared to affect endoxifen (END) concentration. In addition, CYP2D6 polymorphisms potentially influenced 4–hydroxytamoxifen (4OHT) concentrations through a 4OHT subpathway in CYP3A5–poor metabolizer [PM] group.

Methods

• This study entailed one hundred and thirty-four Thai breast cancer patients from the Thai Tamoxifen Project undergoing TAM treatment who met the inclusion/exclusion criteria.
• High-performance liquid chromatography was employed to assess plasma samples for the concentrations of TAM and its metabolites.
• Furthermore, the data were presented as actual values and metabolic ratios (MR).
• Kruskal–Wallis or Mann–Whitney U test, including the simple main effects analysis, the hypotheses were tested.

Results

• Stage 0–IV breast cancer was detected in the patients.
• 51.6±11.6 years and 24.0±4.3 were the mean age and body mass index.
• It was noted that 53.0% of them were premenopausal, 10.4% were perimenopausal and 36.6% were postmenopausal.
• On the other hand, 23.1% were CYP2D6-EM/CYP3A5-EM and 20.9% carried only CYP2D6 and CYP3A5 incomplete alleles.
• 374.7 (interquartile range [IQR] 230.2) ng/mL, 1,064.9 (IQR 599.6) ng/mL, 54.5 (IQR 52.5) ng/mL and 5.0 (IQR 3.1) ng/mL were the median concentrations of TAM, NDMT, END and 4OHT.
• Within the CYP2D6 phenotype (p=0.594), MR (TAM-NDMT) and MR (NDMT-END) were statistically different (p=0.013 and p=0.014, respectively), while MR (4OHT-END) was not statistically different.
• Within the CYP2D6 phenotype (p=0.079)MR (TAM-4OHT) was not statistically different, but it was potentially different from CYP3A5-PM (p=0.056).
• No statistical difference was noticed for any of the MR within the CYP3A5 phenotype.