Association Between Trajectories of Prescription Opioid Use and Risk of Opioid Use Disorder and Overdose Among US Nonmetastatic Breast Cancer Survivors

Abstract

Abstract 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 2.5 years after breast cancer therapy initiation 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 38,265 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] = 4.46 [95% CI = 3.09–6.43]), very low dose (5–25 MME; 15.60 [10.74–22.67]), and moderate dose (51–90 MME; 58.55 [39.92–85.86]). For 9,558 survivors with adjuvant chemotherapy, 3 trajectories were associated with higher OUD/overdose risks compared with early discontinuation: minimal dose (aHR = 3.80 [95% CI = 1.98–7.32]), low dose (26–50 MME; 11.66 [6.01–22.61]), and high dose (91–150 MME; 16.49 [5.90-46.09]). For 3,550 survivors with neoadjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 5.60 [95% CI = 1.91–16.45]) compared with minimal-dose use. Conclusions Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, moderate-dose and high-dose opioid use were associated with 17- to 59-fold higher OUD/overdose risk. For females receiving neoadjuvant chemotherapy, low-dose opioid use was associated with 6-fold higher OUD/overdose risk compared with minimal-dose use. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).