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-HT_2B receptor and TRPV-1.

中文翻译：

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曲马多的使用与乳腺癌患者术后结局增强相关：一项体外验证性回顾性临床研究

背景

术后镇痛药对癌症手术后肿瘤学结局的影响越来越引起人们的关注。我们研究了曲马多对乳腺癌术后复发和死亡率的影响，并探索了曲马多影响体外培养的乳腺癌细胞的机制。

方法

回顾了2005年11月至2010年12月在韩国的Severance医院接受乳腺癌手术的患者的电子病历。使用Cox回归分析来确定与术后复发和死亡率相关的因素。我们使用倾向得分匹配进行灵敏度测试，以调整选择偏向。此外，我们通过评估细胞生存力，克隆形成测定和体外细胞周期分析，研究了曲马多对人乳腺癌细胞（密歇根州癌症基金会7 [MCF-7]）的影响。

结果

在2588名乳腺癌患者中，有36.4％接受了曲马多治疗。接受曲马多的患者复发风险降低了0.71倍，死亡率降低了0.56倍。MCF-7细胞活力测定表明，曲马多具有抑制细胞周期，抑制菌落形成以及调节雌激素和孕激素受体的抗增殖作用。曲马多通过减少5-羟色胺（HT）_2B受体和瞬时受体电位vanilloid-1的表达，通过细胞外信号调节激酶诱导MCF-7细胞凋亡。

结论

乳腺癌手术后，接受曲马多的患者术后复发和死亡的风险降低。曲马多的抗肿瘤作用似乎涉及抑制增殖，诱导细胞凋亡以及对5-HT _2B受体和TRPV-1的影响。