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Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation

 Myoung H. Kim  ;  Ju E. Oh  ;  Seho. Park  ;  Joo H. Kim  ;  Ki Y. Lee  ;  Sun J. Bai  ;  Hyunjik Song  ;  Hye J. Hwang  ;  Dong W. Kim  ;  Young C. Yoo 
 BRITISH JOURNAL OF ANAESTHESIA, Vol.123(6) : 865-876, 2019 
Journal Title
Issue Date
Adenocarcinoma/surgery* ; Adult ; Aged ; Analgesics, Opioid/pharmacology* ; Apoptosis/drug effects ; Breast/drug effects ; Breast/surgery ; Breast Neoplasms/surgery* ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Female ; Humans ; In Vitro Techniques ; MCF-7 Cells ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control* ; Postoperative Complications/prevention & control* ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Tramadol/pharmacology* ; Treatment Outcome ; Tumor Cells, Cultured
analgesics ; apoptosis ; breast cancer ; cancer surgery ; mortality ; recurrence ; tramadol
BACKGROUND: There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. METHODS: Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. RESULTS: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. CONCLUSIONS: After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Hwa(김명화) ORCID logo https://orcid.org/0000-0003-4723-9425
Park, Se Ho(박세호) ORCID logo https://orcid.org/0000-0001-8089-2755
Bai, Sun Joon(배선준) ORCID logo https://orcid.org/0000-0001-5027-3232
Oh, Ju Eun(오주은)
Yoo, Young Chul(유영철) ORCID logo https://orcid.org/0000-0002-6334-7541
Lee, Ki Young(이기영) ORCID logo https://orcid.org/0000-0003-4893-3195
Hwang, Hye Jeong(황혜정) ORCID logo https://orcid.org/0000-0001-5144-3432
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