Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Breast Cancer Res Treat. 2012 Apr;132(3):1107-18. doi: 10.1007/s10549-011-1893-4. Epub 2011 Dec 30.
Tamoxifen decreases breast cancer recurrence, mortality, and breast cancer risk in high-risk women. Despite these proven benefits, tamoxifen use is often limited due to side effects. We identified predictors of tamoxifen-induced side effects based on clinical variables and serum tamoxifen metabolite biomarkers in a cross-sectional study of patients taking tamoxifen. We enrolled 241 women and collected data on demographics, tamoxifen use and side effects, as well as potential clinical and serum predictors. We used logistic regression models and adjusted for age, body mass index, ethnicity, education, prior post-menopausal hormone therapy (HT), tamoxifen duration, and endoxifen levels to identify factors associated with side effects. Common tamoxifen attributed side effects were hot flashes (64%), vaginal dryness (35%), sleep problems (36%), weight gain (6%), and depression, irritability or mood swings (6%). In multi-variate models, tamoxifen duration, age, prior post-menopausal HT, and endoxifen levels all predicted side effects. Women who had been on tamoxifen for >12 months were less likely to report side effects (OR 0.15, 95% CI 0.04-0.58) or severe side effects (OR 0.05, 95% CI 0.005-0.58) compared to women on tamoxifen for <12 months. Compared to women younger than 50, women who were age 60-70 and older than 70 were less likely to report side effects (OR 0.22, 95% CI 0.03-1.35; OR 0.13, 95% CI 0.01-0.99; respectively). Women who previously took post-menopausal HT were more likely to report severe side effects. Women with higher endoxifen levels were more likely to report side effects (OR 1.67, 95% CI 1.01-2.77 per standard deviation increase in endoxifen). Clinicians should consider closely monitoring adherence in women taking tamoxifen, especially in younger women, and women who previously took HT. The association between endoxifen levels and side effects is consistent with the data that suggest that endoxifen is the most highly active metabolite of tamoxifen.
他莫昔芬可降低高危女性的乳腺癌复发率、死亡率和乳腺癌风险。尽管有这些已证实的益处，但由于副作用，他莫昔芬的使用常常受到限制。我们在一项服用他莫昔芬的患者的横断面研究中，根据临床变量和血清他莫昔芬代谢物生物标志物，确定了他莫昔芬诱导的副作用的预测因素。我们纳入了 241 名女性，收集了人口统计学、他莫昔芬使用和副作用以及潜在的临床和血清预测因素的数据。我们使用逻辑回归模型，并根据年龄、体重指数、种族、教育程度、绝经后激素治疗（HT）史、他莫昔芬使用时间和依维莫司水平进行调整，以确定与副作用相关的因素。常见的他莫昔芬相关副作用有热潮红（64%）、阴道干燥（35%）、睡眠问题（36%）、体重增加（6%）和抑郁、易怒或情绪波动（6%）。在多变量模型中，他莫昔芬使用时间、年龄、绝经后 HT 史和依维莫司水平均预测副作用。与使用他莫昔芬<12 个月的女性相比，使用他莫昔芬>12 个月的女性发生副作用（OR 0.15，95%CI 0.04-0.58）或严重副作用（OR 0.05，95%CI 0.005-0.58）的可能性更低。与<50 岁的女性相比，60-70 岁和>70 岁的女性发生副作用的可能性更低（OR 0.22，95%CI 0.03-1.35；OR 0.13，95%CI 0.01-0.99）。曾服用绝经后 HT 的女性更有可能报告严重副作用。依维莫司水平较高的女性发生副作用的可能性更高（依维莫司每增加一个标准差，OR 1.67，95%CI 1.01-2.77）。临床医生应密切监测服用他莫昔芬的女性，尤其是年轻女性和曾服用 HT 的女性的用药依从性。依维莫司水平与副作用之间的关联与提示依维莫司是他莫昔芬最具活性代谢物的数据一致。
