Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors

Breast Cancer Res Treat. 2024 Apr;204(3):561-577. doi: 10.1007/s10549-023-07205-6. Epub 2024 Jan 8.


Purpose: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type.

Methods: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type.

Results: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant.

Conclusions: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Keywords: Breast cancer; Medicare; Opioid overdose; Opioid use disorder; Prescription opioid.

MeSH terms

  • Aged
  • Analgesics, Opioid / adverse effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / epidemiology
  • Cancer Survivors*
  • Drug Overdose* / drug therapy
  • Drug Overdose* / epidemiology
  • Endrin / analogs & derivatives*
  • Female
  • Humans
  • Medicare
  • Opioid-Related Disorders* / complications
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / epidemiology
  • Prescriptions
  • Retrospective Studies
  • Survivors
  • United States / epidemiology


  • Analgesics, Opioid
  • MME
  • Endrin