Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Québec, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada.
Cancer. 2022 Jun 15;128(12):2339-2347. doi: 10.1002/cncr.34208. Epub 2022 Apr 1.
Current guidelines recommend the treatment of hormone receptor-positive breast cancer with aromatase inhibitors (AIs) and tamoxifen in the adjuvant setting. Some observational studies have raised concerns that tamoxifen may be associated with an increased risk of Parkinson disease (PD). However, no studies have directly compared the risk of PD between AIs and tamoxifen in women diagnosed with breast cancer.
Using the UK Clinical Practice Research Datalink, the authors assembled a cohort of women newly diagnosed with breast cancer and newly treated with either AIs or tamoxifen between January 1, 1995, and December 31, 2017. Patients were followed 1 year after treatment initiation (ie, a 1-year lag) until an incident diagnosis of PD or were censored at death from any cause, the date of transfer out of the practice, or the end of the study period (December 31, 2018). Cox proportional hazards models with inverse probability of treatment weights were used to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for PD comparing AIs with tamoxifen and accounting for more than 30 confounders.
In all, 30,140 women with nonmetastatic breast cancer were identified: 13,838 initiated AIs, and 16,302 initiated tamoxifen. Compared with tamoxifen, AIs were not associated with an increased risk of PD (HR, 0.94; 95% CI, 0.60-1.47). Consistent results were observed across all secondary and sensitivity analyses.
In this large observational study, the use of AIs, in comparison with tamoxifen, was not associated with an increased risk of PD in women diagnosed with nonmetastatic breast cancer in a real-world setting.
Previous studies have indicated that tamoxifen may increase the risk of Parkinson disease in the treatment of breast cancer. However, no studies have directly compared the risk of Parkinson disease between aromatase inhibitors and tamoxifen. This study included 30,140 women diagnosed with breast cancer and treated with aromatase inhibitors or tamoxifen. Overall, compared with tamoxifen, aromatase inhibitors were not associated with an increased risk of Parkinson disease in women diagnosed with breast cancer. This study provides an important addition to the comparative safety profile of aromatase inhibitors and tamoxifen in the treatment of breast cancer.
目前的指南建议在辅助治疗中使用芳香化酶抑制剂（AIs）和他莫昔芬治疗激素受体阳性乳腺癌。一些观察性研究引起了人们的担忧，即他莫昔芬可能会增加帕金森病（PD）的风险。然而，尚无研究直接比较在诊断为乳腺癌的女性中，AIs 与他莫昔芬治疗 PD 的风险。
作者利用英国临床实践研究数据链接，组建了一个队列，其中包括 1995 年 1 月 1 日至 2017 年 12 月 31 日期间新诊断为乳腺癌且新接受 AIs 或他莫昔芬治疗的女性患者。在治疗开始后 1 年（即 1 年潜伏期）对患者进行随访，直到出现 PD 确诊病例，或者患者因任何原因死亡、转出实践、或研究期结束（2018 年 12 月 31 日）。使用逆概率治疗加权的 Cox 比例风险模型，比较了 AIs 与他莫昔芬治疗的 PD 风险加权危险比（HR）和 95%置信区间（CI），并考虑了 30 多个混杂因素。
共纳入 30140 例非转移性乳腺癌女性患者：13838 例起始 AIs 治疗，16302 例起始他莫昔芬治疗。与他莫昔芬相比，AIs 并未增加 PD 风险（HR，0.94；95%CI，0.60-1.47）。所有二次分析和敏感性分析均得到一致结果。
在这项大型观察性研究中，与他莫昔芬相比，在真实世界环境中，非转移性乳腺癌女性使用 AIs 治疗与 PD 风险增加无关。
先前的研究表明，在治疗乳腺癌时，他莫昔芬可能会增加帕金森病的风险。然而，尚无研究直接比较芳香化酶抑制剂和他莫昔芬治疗 PD 的风险。这项研究纳入了 30140 例诊断为乳腺癌且接受芳香化酶抑制剂或他莫昔芬治疗的女性。总体而言，与他莫昔芬相比，在诊断为乳腺癌的女性中，芳香化酶抑制剂与帕金森病风险增加无关。这项研究为芳香化酶抑制剂和他莫昔芬在治疗乳腺癌方面的相对安全性概况提供了重要补充。
