Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.
Ann Oncol. 2018 Mar 1;29(3):744-748. doi: 10.1093/annonc/mdx822.
A large trial of postmenopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in postmenopausal women with breast cancer.
Using the UK Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly treated with either AIs or tamoxifen between 1 January 1996 and 30 September 2015, with follow-up until 30 September 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by 1 year for latency considerations.
A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100 000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (P-heterogeneity = 0.54), and time since initiation (P-heterogeneity = 0.66).
In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.
一项针对绝经后乳腺癌女性的大型试验报告称，与辅助治疗中的他莫昔芬相比，芳香酶抑制剂（AIs）在结直肠癌事件方面存在不平衡。这一意外信号是在随机分组后 3 年内观察到的。迄今为止，尚无观察性研究在临床实践的自然环境中研究这一重要的安全性问题。因此，本研究的目的是确定与他莫昔芬相比，AIs 是否会增加绝经后乳腺癌女性的结直肠癌风险。
使用英国临床实践研究数据链接，我们确定了至少 55 岁的女性，她们在 1996 年 1 月 1 日至 2015 年 9 月 30 日期间新接受 AIs 或他莫昔芬治疗，随访至 2016 年 9 月 30 日。使用高维倾向评分调整的 Cox 比例风险模型估计与 AIs 相比他莫昔芬的结直肠癌发病风险的危险比（HR）及其 95%置信区间（CI），总体上、按累积使用时间和起始时间后时间计算。所有暴露均滞后 1 年以考虑潜伏期。
共有 9701 名和 8893 名患者开始使用 AI 和他莫昔芬作为一线激素治疗（中位随访时间分别为 2.4 年和 2.9 年）。与他莫昔芬相比，AIs 并未增加结直肠癌的风险（两组的发病率均为每 100000 人年 150 例；调整后的 HR：0.90，95%CI：0.53-1.52）。同样，没有证据表明与累积使用时间（P 异质性=0.54）和起始时间后时间（P 异质性=0.66）有关。
在这项首次基于人群的研究中，使用 AIs 与结直肠癌风险增加无关。这些发现应该让相关利益相关者放心。
