The association between perioperative opioids and breast cancer recurrence: a narrative review of the literature

Abstract

Background and Objective Opioid use disorder is an evolving crisis, and 17.2% of postsurgical patients continue to fill an opioid prescription one year after surgery. Preclinical studies suggest perioperative opioid use, defined here as opioids used in the setting of operative pain, may be linked to inferior oncologic outcomes. If this were true, opioid minimization strategies for surgical patients may reduce opioid-related deaths in more than one way. This review aims to describe the association between perioperative opioid use and breast cancer recurrence. Methods On November 1, 2021, we searched the Ovid and EMBASE databases for the terms “breast neoplasm”, “opioid analgesics”, “neoplasm recurrence”, and “neoplasm metastasis”. Of the 350 articles retrieved, 11 met our inclusion criteria. The review was undertaken using the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) checklist for quality. Key Content and Findings Clinical studies report no clear association between perioperative opioid use and local or distant breast cancer recurrence. Mixed results were found when assessing perioperative opioid use and overall survival. Multiple studies paradoxically found opioid use to be associated with lower recurrence rates, despite higher mortality rates. Most studies showed no difference in recurrence or survival in breast cancer surgery patients who did or did not receive opioid-containing analgesia, although most findings were limited by study design and low event rates in patients with breast cancer. Conclusions The lack of a clear connection between perioperative opioid use and breast cancer recurrence contradicts some preclinical data, which describes mechanisms through which opioids upregulate tumor proliferation which might worsen oncologic outcomes. Existing clinical literature is limited to mostly retrospective studies in patients with predominantly early-stage breast cancers, with low event rates. Given the worsening opioid epidemic and preclinical study findings, opioid minimization strategies should still be explored. Future work should be prospective and examine cancer recurrence in high-risk patients with more advanced tumor pathologies.

Comparison of the effects of sufentanil-dominant anaesthesia/analgesia and epidural anaesthesia/analgesia on postoperative immunological alterations, stress responses and prognosis in open hepatectomy: a randomized trial

“…However, in cancer patients, opioids often exert immunosuppressive effects, including modulating cellular and humoral responses, inhibiting natural killer (NK) cell cytotoxicity ( 16 ), directly acting on tumour cells, stimulating angiogenesis and interacting with the μ-receptor ( 17 , 18 ), in the regulation of tumour growth and metastasis. Many preclinical studies and retrospective studies suggest that perioperative opioid use may be linked to cancer-promoting effects and lead to inferior oncologic outcomes ( 19 ). However, the majority of research focusing on the immune system has involved in vitro or animal studies and clinical retrospective studies, which have low translational value, with most evidence deriving from laboratory and retrospective clinical studies ( 19 ).…”

“…Many preclinical studies and retrospective studies suggest that perioperative opioid use may be linked to cancer-promoting effects and lead to inferior oncologic outcomes ( 19 ). However, the majority of research focusing on the immune system has involved in vitro or animal studies and clinical retrospective studies, which have low translational value, with most evidence deriving from laboratory and retrospective clinical studies ( 19 ). Well-designed randomized controlled trials (RCTs) are needed to clarify the relationship between cancer recurrence and anaesthesia-related factors.…”