Hormone Laboratory, Haukeland University Hospital, 5020, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
Breast Cancer Res Treat. 2019 Aug;177(1):185-195. doi: 10.1007/s10549-019-05294-w. Epub 2019 May 29.
Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring.
Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC-MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation.
At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4'-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation.
This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data.
他莫昔芬是乳腺癌中一种重要的靶向内分泌治疗药物。然而，他莫昔芬的副作用和早期停药仍然是获得长期他莫昔芬治疗改善预后益处的障碍。预测他莫昔芬副作用的生物标志物仍未确定。本前瞻性基于人群的研究旨在探讨他莫昔芬代谢物浓度作为副作用生物标志物的价值。第二个目的是评估通过药物监测获得的停药率与使用他莫昔芬的药房记录的有效性。
在 6 年期间，从 220 名乳腺癌患者中获得了纵向血清样本、患者报告的结局测量和药房记录。通过 LC-MS/MS 测定血清中他莫昔芬代谢物的浓度。通过逻辑回归和交叉表分析来分析代谢物浓度与副作用之间的关系。为了确定药房记录的有效性，我们将纵向他莫昔芬浓度与通过挪威处方数据库（NorPD）获得的停药率进行了比较。使用多变量 Cox 回归模型来确定停药的预测因素。
在随访的第 2 年，发现阴道干燥与高浓度的他莫昔芬、Z-4'-OHtam 和 tam-NoX 之间存在显著关联。NorPD 在 5 年内显示出 17.9%的他莫昔芬停药率，药物监测也显示出类似的停药率。恶心、阴道干燥和化疗初治状态是他莫昔芬停药的显著危险因素。
这项真实世界数据研究表明，他莫昔芬代谢物浓度的测量可能可以预测乳腺癌患者的阴道干燥，并验证了 NorPD 是一种可靠的依从性数据来源。
