Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2⁺ breast cancer.
Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2 breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of "good clinical practice" should be maintained.
Division of Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands Department of Anesthesiology, Academic Medical Center, Amsterdam, the Netherlands Division of Molecular Pathology and Cancer Genomics Center, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Chris W
CW
Doornebal
Kim
K
Vrijland
Cheei-Sing
CS
Hau
Seth B
SB
Coffelt
Metamia
M
Ciampricotti
Jos
J
Jonkers
Karin E
KE
de Visser
Markus W
MW
Hollmann
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001943:Breast Neoplasms / Q000150:complications* / Q000473:pathology* / Q000523:psychology; D018275:Carcinoma, Lobular / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D009020:Morphine