Purpose

Tamoxifen is part of endocrine therapy in breast cancer treatment. Studies have indicated the use of endoxifen concentrations, tamoxifen active metabolite, to guide tamoxifen efficacy. Three endoxifen thresholds have been suggested (5.9 ng/ml, 5.2 ng/ml and 3.3 ng/ml) for therapeutic drug monitoring (TDM). Our aim was to validate these thresholds and to examine endoxifen exposure with clinical outcome in early-breast cancer patients using tamoxifen.

Methods

Data from 667 patients from the CYPTAM study (NTR1509) were available. Patients were stratified (above or below), according to the endoxifen threshold values for tamoxifen efficacy and tested by Cox regression. Logistic regressions to estimate the probability of relapse and tamoxifen discontinuation were performed.

Results

None of the thresholds showed a statistically significant difference in relapse-free survival: 5.2 ng/ml threshold: hazard ratio (HR): 2.545, 95% confidence interval (CI) 0.912–7.096, p value: 0.074; 3.3 ng/ml threshold: HR: 0.728; 95% CI 0.421–1.258, p value: 0.255. Logistic regression did not show a statistically significant association between the risk of relapse (odds ratio (OR): 0.971 (95% CI 0.923–1.021, p value: 0.248) and the risk for tamoxifen discontinuation (OR: 1.006 95% CI 0.961–1.053, p value: 0.798) with endoxifen concentrations.

Conclusion

Our findings do not confirm the endoxifen threshold values for TDM nor does it allow definition of a novel threshold. These findings indicate a limited value of TDM to guide tamoxifen efficacy.

中文翻译：

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早期乳腺癌中内皮昔芬血清浓度的暴露-反应分析。

目的

他莫昔芬是乳腺癌治疗中内分泌治疗的一部分。研究表明使用内皮西芬浓度，他莫昔芬活性代谢物来指导他莫昔芬的疗效。对于治疗药物监测（TDM），建议使用三个endoxifen阈值（5.9 ng / ml，5.2 ng / ml和3.3 ng / ml）。我们的目的是验证这些阈值，并检查使用他莫昔芬对早期乳腺癌患者的内皮索芬暴露及其临床结局。

方法

已有来自CYPTAM研究（NTR1509）的667名患者的数据。根据他莫昔芬疗效的内皮西芬阈值对患者进行分层（高于或低于），并通过Cox回归进行测试。进行逻辑回归以估计复发和他莫昔芬停药的可能性。

结果

没有一个阈值显示无复发生存率有统计学上的显着差异：5.2 ng / ml阈值：危险比（HR）：2.545，95％置信区间（CI）0.912-7.096，p值：0.074；3.3 ng / ml阈值：HR：0.728；95％CI 0.421–1.258，p值：0.255。Logistic回归未显示复发风险（优势比（OR）：0.971（95％CI 0.923–1.021，p值：0.248））与他莫昔芬停药风险（OR：1.006 95％CI 0.961– 1.053，p值：0.798）与endoxifen浓度。

结论

我们的发现不能确定TDM的内皮西芬阈值，也不能定义新的阈值。这些发现表明TDM指导他莫昔芬疗效的价值有限。