Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer
Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:126 |
|---|---|
| Enthalten in: |
British journal of anaesthesia - 126(2021), 2 vom: 01. Feb., Seite 367-376 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Montagna, Giacomo [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.02.2021 Date Revised 02.02.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bja.2020.10.021 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM317879596 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM317879596 | ||
| 003 | DE-627 | ||
| 005 | 20231225164204.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bja.2020.10.021 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1059.xml |
| 035 | |a (DE-627)NLM317879596 | ||
| 035 | |a (NLM)33220939 | ||
| 035 | |a (PII)S0007-0912(20)30862-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Montagna, Giacomo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.02.2021 | ||
| 500 | |a Date Revised 02.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a RNA-seq | |
| 650 | 4 | |a immunomodulation | |
| 650 | 4 | |a opioid receptor | |
| 650 | 4 | |a opioids | |
| 650 | 4 | |a outcome | |
| 650 | 4 | |a personalised medicine | |
| 650 | 4 | |a recurrence | |
| 650 | 4 | |a survival | |
| 650 | 4 | |a triple-negative breast cancer | |
| 650 | 7 | |a Analgesics, Opioid |2 NLM | |
| 650 | 7 | |a Receptors, Opioid |2 NLM | |
| 700 | 1 | |a Gupta, Hersh V |e verfasserin |4 aut | |
| 700 | 1 | |a Hannum, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Kay See |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jasme |e verfasserin |4 aut | |
| 700 | 1 | |a Scarpa, Joseph R |e verfasserin |4 aut | |
| 700 | 1 | |a Plitas, George |e verfasserin |4 aut | |
| 700 | 1 | |a Irie, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a McCormick, Patrick J |e verfasserin |4 aut | |
| 700 | 1 | |a Fischer, Gregory W |e verfasserin |4 aut | |
| 700 | 1 | |a Morrow, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Mincer, Joshua S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of anaesthesia |d 1946 |g 126(2021), 2 vom: 01. Feb., Seite 367-376 |w (DE-627)NLM000000310 |x 1471-6771 |7 nnns |
| 773 | 1 | 8 | |g volume:126 |g year:2021 |g number:2 |g day:01 |g month:02 |g pages:367-376 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bja.2020.10.021 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 126 |j 2021 |e 2 |b 01 |c 02 |h 367-376 | ||