Breast Cancer Survivors at Highest Opioid Abuse, Overdose Risk

M. Alexander Otto, PA, MMS

March 31, 2023

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Among people living with breast cancer and survivors, long-term prescription opioid use greatly increases the risk of opioid use disorders and overdoses, particularly among those receiving adjuvant endocrine therapy.

Why This Matters

  • Concerns about the risk of long-term opioid therapy for cancer survivors, including people with breast cancer, persist.

  • The study helps define the patients most likely to run into problems with prescription opioids.

  • The analysis helps identify breast cancer survivors at the highest risk for opioid abuse or overdose who may benefit from a referral to a pain clinic to help manage their pain.

Study Design

  • The team linked Medicare and Surveillance, Epidemiology and End Results data to identify nonmetastatic breast cancer survivors who had filled at least one opioid prescription from 2010–2019.

  • The researchers divided the women according to their mean daily dose of morphine milligram equivalents (MME): a minimal dose (<5 MME/d), very low dose (5–25 MME/d), low dose (26–50 MME/d), moderate dose (51–90 MME/d), or high dose (91–150 MME/d).

  • Investigators then calculated the risk of an opioid use disorder or overdose within 2.5 years of initiating breast cancer treatment.

  • They compared the risk of opioid use disorder or overdose among people who continued taking opioids with those who discontinued opioids early.

  • The study included 38,265 women who received systemic endocrine therapy, 9558 who received adjuvant chemotherapy, and 3550 who had received neoadjuvant chemotherapy.

Key Results

  • Overall, 1.03% of women who had received systemic endocrine therapy, 1.49% who had received adjuvant chemotherapy, and 1.61% who had received neoadjuvant chemotherapy had an opioid use disorder or overdose within 2.5 years of initiating breast cancer treatment.

  • Among women receiving endocrine therapy, minimal-dose (adjusted hazard ratio [aHR], 4.46), very-low-dose (aHR, 15.60), and moderate-dose opioids (aHR, 58.55) increased the risk of opioid use disorder or overdose compared with women who discontinued opioids early.

  • For those who had received adjuvant chemotherapy, minimal-dose (aHR, 3.80), low-dose (aHR, 11.66), and high-dose opioids (aHR, 16.49) increased the risk.

  • Low-dose opioid use (aHR, 5.60) increased the risk in the neoadjuvant chemotherapy arm in comparison with minimal-dose use.


  • It's unknown whether women took opioids as prescribed.

  • The databases did not capture relevant sociobehavioral and clinical information, including changes in cancer pain over time, so there may be residual confounding.


  • There was no outside funding for the work.

  • Investigators received grants from Merck Sharp & Dohme, Bristol-Myers Squibb, and the Pharmaceutical Research and Manufacturers of America Foundation. One has a patent pending on a machine learning algorithm for opioid risk prediction. Some investigators were employees of Vertex Pharmaceuticals and Otsuka.

This is a summary of a preprint research study, "Association Between Trajectories of Prescription Opioid Use and Risk of Opioid Use Disorder and Overdose Among US Nonmetastatic Breast Cancer Survivors," led by Ching-Yuan Chang of the University of Florida College of Pharmacy during the study, provided to you by Medscape. The study has not been peer reviewed. The full text can be found at

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who has worked for several major news outlets before joining Medscape and also an MIT Knight Science Journalism fellow. Email:

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