Opioids and breast cancer recurrence: A Danish population-based cohort study

• Type of Material: Article
• Authors: Deirdre Cronin-Fenton, Aarhus University; Uffe Heide-Jørgensen, Aarhus University; Thomas P. Ahern, University of Vermont; Timothy Lash, Emory University; Peer M. Christiansen, Aarhus University; Bent Ejlertsen, Danish Breast Cancer Cooperative Group; Per Sjøgren, Rigshospitalet; Henrik Kehlet, Rigshospitalet; Henrik T. Sørensen, Aarhus University
• Language: English
• Date: 2015-10-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.29532
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 121
• Issue: 19
• Start Page: 3507
• End Page: 3514
• Grant/Funding Information: The work was supported by a grant from the Danish Cancer Society (R73-A4284-13-S17) [HTS]; the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation [HTS]; the Aarhus University Research Foundation [HTS]; the Elvira & Rasmus Riisforts Fonden [DCF]; the Lundbeck Foundation (R167-2013-15861) [DCF]; Susan G. Komen for the Cure (CCR 13264024) [TPA]; Mary Kay Foundation (003-14) [TPA]; and the US National Cancer Institute at the National Institutes of Health (R01CA166825) [TLL, DCF].
• Keywords: risk; opioids; cohort study; breast cancer recurrence; epidemiology; breast cancer
• Research Categories: Health Sciences, Oncology; Health Sciences, Epidemiology

Abstract

Background: Opioids may alter immune function and thereby potentially affect cancer recurrence. We investigated the association between post-diagnosis opioid use and breast cancer recurrence. Methods: We identified incident early-stage breast cancer patients, diagnosed 1996-2008 in Denmark, registered in the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of breast cancer primary surgery and continued until breast cancer recurrence, death, emigration, ten years, or 31 July 2013, whichever occurred first. We used Cox regression models to compute hazard ratios (HRs) and 95% confidence intervals (95%CI) associating breast cancer recurrence with opioid prescription use overall, and by opioid type and strength, immunosuppressive effect, chronic use (>=6 months continuous exposure), and cumulative morphine-equivalent dose, adjusting for confounders. Results: We identified 34,188 patients who together contributed 283,666 person-years of follow-up. There was no association between ever use of opioids and breast cancer recurrence (HRcrude=0.98, 95% CI=0.90 - 1.1, and HRadjusted=1.0, 95% CI=0.92 - 1.1), regardless of opioid type, strength, chronicity of use, and cumulative dose. Breast cancer recurrence rates were lower among users of strong but not weakly immunosuppressive opioids, possibly due to channeling bias among those with high competing risk as mortality was higher among users of this drug type. Conclusions: This large prospective cohort study provided no clinically relevant evidence of an association between opioid prescriptions and breast cancer recurrence. Our findings are important to cancer survivorship, as opioids are frequently used to manage pain associated with comorbid conditions.