Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer Journal Article


Authors: Montagna, G.; Gupta, H. V.; Hannum, M.; Tan, K. S.; Lee, J.; Scarpa, J. R.; Plitas, G.; Irie, T.; McCormick, P. J.; Fischer, G. W.; Morrow, M.; Mincer, J. S.
Article Title: Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer
Abstract: Background: Opioid-induced immunomodulation may be of particular importance in triple-negative breast cancer (TNBC) where an immune response is associated with improved outcome and response to immunotherapy. We evaluated the association between intraoperative opioids and oncological outcomes and explored patterns of opioid receptor expression in TNBC. Methods: Consecutive patients with stage I–III primary TNBC were identified from a prospectively maintained database. Opioid receptor expression patterns in the tumour microenvironment were analysed using publicly available bulk and single-cell RNA-seq data. Results: A total of 1143 TNBC cases were retrospectively analysed. In multivariable analysis, higher intraoperative opioid dose was associated with favourable recurrence-free survival, hazard ratio 0.93 (95% confidence interval 0.88–0.99) per 10 oral morphine milligram equivalents increase (P=0.028), but was not significantly associated with overall survival, hazard ratio 0.96 (95% confidence interval 0.89–1.02) per 10 morphine milligram equivalents increase (P=0.2). Bulk RNA-seq analysis of opioid receptors showed that OPRM1 was nearly non-expressed. Compared with normal breast tissue OGFR, OPRK1, and OPRD1 were upregulated, while TLR4 was downregulated. At a single-cell level, OPRM1 and OPRD1 were not detectable; OPRK1 was expressed mainly on tumour cells, whereas OGFR and TLR4 were more highly expressed on immune cells. Conclusions: We found a protective effect of intraoperative opioids on recurrence-free survival in TNBC. Opioid receptor expression was consistent with a net protective effect of opioid agonism, with protumour receptors either not expressed or downregulated, and antitumour receptors upregulated. In this era of personalised medicine, efforts to differentiate the effects of opioids across breast cancer subtypes (and ultimately individual patients) should continue. © 2020 British Journal of Anaesthesia
Keywords: survival; recurrence; outcome; immunomodulation; opioids; opioid receptor; triple-negative breast cancer; rna-seq; personalised medicine
Journal Title: British Journal of Anaesthesia
Volume: 126
Issue: 2
ISSN: 0007-0912
Publisher: Oxford University Press  
Date Published: 2021-02-01
Start Page: 367
End Page: 376
Language: English
DOI: 10.1016/j.bja.2020.10.021
PUBMED: 33220939
PROVIDER: scopus
PMCID: PMC8014943
DOI/URL:
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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MSK Authors
  1. Monica Morrow
    772 Morrow
  2. George Plitas
    107 Plitas
  3. Kay See   Tan
    241 Tan
  4. Gregory Walter Fischer
    40 Fischer
  5. Takeshi Irie
    14 Irie
  6. Margaret L Hannum
    17 Hannum
  7. Giacomo Montagna
    100 Montagna
  8. Joshua Samuel Mincer
    23 Mincer
  9. Jasme Lee
    32 Lee