Hsu Fan-Gen, Hsieh Yow-Wen, Sheu Ming-Jyh, Lin Che-Chen, Lin Cheng-Li, Hsu Chung Y, Lee Chang-Yin, Chang Mei-Yin, Chang Kuang-Hsi
School of Pharmacy, China Medical University, Taichung, Taiwan.
Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan.
PLoS One. 2017 Mar 14;12(3):e0173089. doi: 10.1371/journal.pone.0173089. eCollection 2017.
Several case reports have indicated that tamoxifen induced acute pancreatitis (AP); but no pharmacoepidemiological data support the claim. Therefore, we investigated whether tamoxifen use is correlated with the risk of AP in patients with breast cancer.
This population-based cohort study used the Taiwan National Health Insurance Research Database. A cohort of 22 005 patients aged ≥20 years with breast cancer from January 1, 2000 to December 31, 2009 was identified and the date of cancer diagnosis was set as the index date. The end point was developing AP during the follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to determine the correlation between the risk of AP and tamoxifen use. Because the drug use varied over time, it was measured as a time-dependent covariate in the Cox proportional hazard model. The same approaches were applied in PS-matched cohorts.
After adjustment for covariates and medication use including fluorouracil and doxorubicin, the risk of AP was not significant between tamoxifen users and tamoxifen nonusers (adjusted HR = 0.94, 95% CI = 0.74-1.19) in the non-matching cohorts. The results revealed no dose-response trend between tamoxifen use and the risk of AP (adjusted HR = 0.98, 95% CI = 0.96-1.00). The comorbidities DM and gallstones were associated with a significantly increased risk of AP. Similar trends were observed in PS-matched cohorts.
No significant correlation was observed between tamoxifen use and the risk of AP in patients with breast cancer.
多项病例报告表明他莫昔芬可诱发急性胰腺炎（AP）；但尚无药物流行病学数据支持这一说法。因此，我们调查了乳腺癌患者使用他莫昔芬是否与AP风险相关。
这项基于人群的队列研究使用了台湾国民健康保险研究数据库。确定了一组2000年1月1日至2009年12月31日年龄≥20岁的22005例乳腺癌患者，并将癌症诊断日期设定为索引日期。终点是随访期间发生AP。评估风险比（HR）和95%置信区间（CI）以确定AP风险与他莫昔芬使用之间的相关性。由于药物使用随时间变化，在Cox比例风险模型中将其作为时间依赖性协变量进行测量。在倾向评分匹配队列中应用相同的方法。
在非匹配队列中，在调整了包括氟尿嘧啶和阿霉素在内的协变量和药物使用后，他莫昔芬使用者和非使用者之间的AP风险无显著差异（调整后HR = 0.94，95%CI = 0.74 - 1.19）。结果显示他莫昔芬使用与AP风险之间无剂量反应趋势（调整后HR = 0.98，95%CI = 0.96 - 1.00）。合并症糖尿病和胆结石与AP风险显著增加相关。在倾向评分匹配队列中观察到类似趋势。
乳腺癌患者使用他莫昔芬与AP风险之间未观察到显著相关性。
