Abstract：
UNASSIGNED: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dosage. However, the clinical significance of endoxifen on the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication.
UNASSIGNED: The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff.
UNASSIGNED: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics.
UNASSIGNED: Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.
UNASSIGNED: The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff.
UNASSIGNED: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics.
UNASSIGNED: Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.
摘要：
■他莫昔芬的代谢受各种细胞色素p450酶的影响，包括CYP2D6和CYP2C19，导致内西芬水平的变化，即使使用相同的他莫昔芬剂量。然而,内西芬对乳腺癌患者预后的临床意义仍存在争议。这项研究旨在阐明多西芬水平与他莫昔芬停药（RFSt）的无复发生存率的相关性。代表他莫昔芬本身的RFS，乳腺癌患者的预后，并确定合适的临界值。
■该研究包括478名乳腺癌患者，和他莫昔芬及其代谢物，包括多西芬,使用液相色谱-串联质谱(LC-MS/MS)测量。用最大选择的等级统计确定最佳截止值。基于该截止值进行生存分析和Cox回归。
■21.00ng/mL的内昔芬水平是预测的最佳截止值。生存分析显示，低内皮昔芬组（≤21.00ng/mL）和高内皮昔芬组（>21.00ng/mL）之间的RFSt有统计学意义的差异（对数秩检验，p=0.032)。在低和高内昔芬组中，RFSt的10年概率为83.2％（95％CI，77.0-89.9％）和88.3％（95％CI，83.3-93.5％），分别。多变量Cox比例风险回归表明，内西芬浓度是影响预后的重要因素，与其他临床特征进行了调整。
■Endoxifen可以作为适当的他莫昔芬治疗的标志，和21.00ng/mL的endoxifen截止值可能有利于预后。基于这个界限，治疗药物监测将有利于显示次优浓度的患者。
■该研究包括478名乳腺癌患者，和他莫昔芬及其代谢物，包括多西芬,使用液相色谱-串联质谱(LC-MS/MS)测量。用最大选择的等级统计确定最佳截止值。基于该截止值进行生存分析和Cox回归。
■21.00ng/mL的内昔芬水平是预测的最佳截止值。生存分析显示，低内皮昔芬组（≤21.00ng/mL）和高内皮昔芬组（>21.00ng/mL）之间的RFSt有统计学意义的差异（对数秩检验，p=0.032)。在低和高内昔芬组中，RFSt的10年概率为83.2％（95％CI，77.0-89.9％）和88.3％（95％CI，83.3-93.5％），分别。多变量Cox比例风险回归表明，内西芬浓度是影响预后的重要因素，与其他临床特征进行了调整。
■Endoxifen可以作为适当的他莫昔芬治疗的标志，和21.00ng/mL的endoxifen截止值可能有利于预后。基于这个界限，治疗药物监测将有利于显示次优浓度的患者。
