title: Opioids and breast cancer recurrence: A Danish population-based cohort study.
abstract: BACKGROUND
  Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
authors.forename: Deirdre P
authors.initials: DP
authors.lastname: Cronin-Fenton
authors.affiliation: Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Heide-Jørgensen
authors.affiliation: Departments of Surgery and Biochemistry, University of Vermont, Burlington, Vermont.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Ahern
authors.affiliation: Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.|Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Lash
authors.affiliation: Breast and Endocrine Section, Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark.|Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
authors.forename: Peer M
authors.initials: PM
authors.lastname: Christiansen
authors.affiliation: Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.|Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Section of Palliative Medicine, Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Sjøgren
authors.affiliation: Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
authors.affiliation: Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
authors.forename: Henrik T
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local
chemical_list: D000701:Analgesics, Opioid
keywords: breast cancer; breast cancer recurrence; cohort study; epidemiology; opioids; risk