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CXCL8-CXCR1/2 轴在三阴性乳腺癌新辅助化疗中的价值:一项回顾性初步研究。

Value of CXCL8-CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study.

机构信息

Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 399 Ling-Ling Road, Shanghai, 200032, People's Republic of China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

出版信息

Breast Cancer Res Treat. 2020 Jun;181(3):561-570. doi: 10.1007/s10549-020-05660-z. Epub 2020 May 2.

Abstract

BACKGROUND

In this study we investigate the prediction and prognostic value of CXCL8-CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery.

METHODS

A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation.

RESULTS

Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2- patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900-0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933-4.949; CXCR1/2++, HR 3.466, 95% CI 1.569-7.655, CXCR1/2- was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome.

CONCLUSIONS

This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8-CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.

摘要

背景

本研究旨在探讨 CXCL8-CXCR1/2 轴在接受标准根治性手术后接受新辅助化疗(NAC)的三阴性乳腺癌(TNBC)患者中的预测和预后价值。

方法

本研究共纳入 303 例 TNBC 患者。所有患者均接受每周紫杉醇加卡铂(PC)的 NAC 方案。通过酶联免疫吸附试验(ELISA)在基线和手术时测量血清 CXCL8 水平。免疫组织化学用于检测 NAC 后残余肿瘤中 CXCR1 和 CXCR2 的表达。研究变量与治疗反应之间的相关性,并进行 Cox 比例风险回归分析进行预后评估。

结果

在 303 例患者中,103 例(34.0%)患者在 NAC 完成后出现病理完全缓解(pCR)。在 CXCR1/2+患者中,NAC 后 CXCL8 水平显著升高,而在 CXCR1/2-患者中 NAC 后 CXCL8 水平降低。手术时 CXCL8 水平较低的患者更有可能观察到更高的 pCR 率(P=0.004,HR 0.939,95%CI 0.900-0.980)。在多变量生存模型中,CXCR1/2 表达是生存的独立预后因素(CXCR1/2+,HR 2.149,95%CI 0.933-4.949;CXCR1/2++,HR 3.466,95%CI 1.569-7.655,以 CXCR1/2-作为参考;P=0.003)。CXCR1/2 表达水平较高的患者更有可能出现不良结局。

结论

本研究有助于阐明血清 CXCL8 水平对预测 TNBC 患者 pCR 的价值,以及 NAC 后非 pCR 患者 CXCR1/2 的预后表现。CXCL8-CXCR1/2 可能在为晚期 TNBC 调整和修改 NAC 策略方面发挥重要作用,但需要进一步的证实性研究。

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