Cronin-Fenton Deirdre P, Heide-Jørgensen Uffe, Ahern Thomas P, Lash Timothy L, Christiansen Peer M, Ejlertsen Bent, Sjøgren Per, Kehlet Henrik, Sørensen Henrik T
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
Departments of Surgery and Biochemistry, University of Vermont, Burlington, Vermont.
Cancer. 2015 Oct 1;121(19):3507-14. doi: 10.1002/cncr.29532. Epub 2015 Jul 24.
Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence.
Patients with incident, early stage breast cancer who were diagnosed during 1996 through 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months of continuous exposure), and cumulative morphine-equivalent dose, adjusting for confounders.
In total, 34,188 patients were identified who, together, contributed 283,666 person-years of follow-up. There was no association between ever-use of opioids and breast cancer recurrence (crude hazard ratio, 0.98; 95% confidence interval, 0.90-1.1; adjusted hazard ratio, 1.0; 95% confidence interval, 0.92-1.1), regardless of opioid type, strength, chronicity of use, or cumulative dose. Breast cancer recurrence rates were lower among users of strongly (but not weakly) immunosuppressive opioids, possibly because of channeling bias among those with a high competing risk, because mortality was higher among users of this drug type.
This large, prospective cohort study provided no clinically relevant evidence of an association between opioid prescriptions and breast cancer recurrence. The current findings are important to cancer survivorship, because opioids are frequently used to manage pain associated with comorbid conditions.
阿片类药物可能会改变免疫功能,从而潜在地影响癌症复发。作者调查了确诊后使用阿片类药物与乳腺癌复发之间的关联。
从丹麦乳腺癌合作组登记处识别出1996年至2008年期间在丹麦确诊的初发早期乳腺癌患者。从丹麦国家处方登记处确定阿片类药物处方。随访从乳腺癌初次手术日期开始,持续至乳腺癌复发、死亡、移民、满10年或2013年7月31日,以先发生者为准。使用Cox回归模型计算总体以及按阿片类药物类型、强度、免疫抑制作用、长期使用(连续暴露≥6个月)和吗啡等效累积剂量将乳腺癌复发与阿片类药物处方使用相关联的风险比和95%置信区间,并对混杂因素进行校正。
总共识别出34188例患者,他们总共提供了283666人年的随访。无论阿片类药物类型、强度、使用时长或累积剂量如何,曾经使用阿片类药物与乳腺癌复发之间均无关联(粗风险比,0.98;95%置信区间,0.90 - 1.1;校正后风险比,1.0;95%置信区间,0.92 - 1.1)。在使用强效(而非弱效)免疫抑制阿片类药物的患者中,乳腺癌复发率较低,这可能是由于高竞争风险患者中的渠道偏倚,因为该药物类型使用者的死亡率较高。
这项大型前瞻性队列研究未提供阿片类药物处方与乳腺癌复发之间存在临床相关关联的证据。当前的研究结果对癌症幸存者很重要,因为阿片类药物经常用于管理与合并症相关的疼痛。