Health Research Institute, Kaiser Permanente Washington, Seattle, Washington.
Department of Pharmacy, University of Washington, Seattle, Washington.
Pharmacoepidemiol Drug Saf. 2019 May;28(5):740-753. doi: 10.1002/pds.4779. Epub 2019 Apr 3.
Opioids may increase cancer risk and progression through multiple pathways. Our objective was to estimate the association between chronic opioid use and risk of second breast cancer events (SBCEs).
Cohort study of women greater than or equal to 18 years, diagnosed with early stage breast cancer between January 1, 1990, and December 31, 2008, and enrolled in a large health plan for 1+ years before and after (unless died) diagnosis. SBCEs were defined as evidence of recurrence or second primary breast cancer in the medical chart. Chronic opioid use was defined as 75+ days of use in any moving 90-day window after breast cancer diagnosis and varied to 150+ days in a 180-day window in a sensitivity analysis. Using Cox proportional hazards models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for SBCE and components of SBCE by chronic opioid use.
Almost 10% met the criteria for chronic use and almost a third of users were taking opioids for greater than 3 years. Risk of SBCEs (HR = 1.20; 95% CI, 0.85-1.70), including second primary breast cancer (HR = 1.38; 95% CI, 0.71-2.70), was nonsignificantly higher among chronic users vs nonchronic/nonusers. The HR for recurrence was 1.14 (95% CI, 0.76-2.70). Results of the sensitivity analyses on longer opioid use does support an association with SBCE or recurrence.
This first US-based study on chronic opioid use and cancer outcomes provides some reassurance on safety. However, the question warrants further exploration in other populations and settings.
阿片类药物可能通过多种途径增加癌症风险和进展。我们的目的是评估慢性阿片类药物使用与第二乳腺癌事件(SBCE)风险之间的关联。
这是一项队列研究,纳入了 1990 年 1 月 1 日至 2008 年 12 月 31 日期间被诊断为早期乳腺癌且年龄大于等于 18 岁的女性,并在诊断前和诊断后(除非死亡)至少 1 年加入了一个大型健康计划。SBCE 定义为医疗记录中复发或第二原发性乳腺癌的证据。慢性阿片类药物使用定义为在乳腺癌诊断后任何 90 天移动窗口中使用 75 天以上,在敏感性分析中,在 180 天窗口中使用 150 天以上。使用 Cox 比例风险模型,我们根据慢性阿片类药物使用情况估计了 SBCE 和 SBCE 组成部分的风险比(HR)和 95%置信区间(CI)。
近 10%的患者符合慢性使用标准,近三分之一的患者使用阿片类药物的时间超过 3 年。慢性使用者与非慢性/非使用者相比,SBCE 风险(HR=1.20;95%CI,0.85-1.70),包括第二原发性乳腺癌(HR=1.38;95%CI,0.71-2.70),无统计学显著升高。复发的 HR 为 1.14(95%CI,0.76-2.70)。更长时间使用阿片类药物的敏感性分析结果确实支持与 SBCE 或复发的关联。
这是第一项关于慢性阿片类药物使用与癌症结局的美国研究,为安全性提供了一些保证。然而,这个问题需要在其他人群和环境中进一步探讨。