三阴性乳腺癌术前化疗效果预测新标志
由巨噬细胞等免疫细胞分泌的白细胞介素-8（IL-8）又称趋化因子配体8（CXCL8），与CXCL8受体α（又称CXCR1）和CXCL8受体β（又称CXCR2）结合以后，可以趋化中性粒细胞，从而调节炎症反应，而且还有很强的促肿瘤血管生成作用，对于癌细胞的生长、转移、耐药具有重要意义。不过，CXCL8、CXCR1、CXCR2对于三阴性乳腺癌术前新辅助化疗的意义尚不明确。
2020年5月2日，施普林格自然旗下《乳腺癌研究与治疗》在线发表复旦大学附属肿瘤医院王若曦、吉芃、龚悦、邵志敏、陈盛等学者的研究报告，探讨了CXCL8、CXCR1、CXCR2对于三阴性乳腺癌标准根治术前新辅助化疗近期疗效预测和远期生存预后的价值。
该研究对2009年1月～2015年7月复旦大学附属肿瘤医院标准根治术前接受每周紫杉醇＋卡铂新辅助化疗的303例三阴性乳腺癌患者进行回顾分析，化疗前和术前通过酶联免疫吸附测定血清CXCL8水平，通过免疫组织化学测定术前新辅助化疗后残留肿瘤患者的CXCR1和CXCR2表达。通过多因素比例风险回归模型，分析近期疗效预测和远期生存预后的相关因素。
结果，术前新辅助化疗后病理完全缓解患者103例（34.0%）
CXCR1/2阳性患者的CXCL8水平显著较高
CXCR1/2阴性患者的CXCL8水平显著较低
CXCL8水平较低与较高的患者相比，病理完全缓解率显著较高（P=0.004，风险比：0.939，95%置信区间：0.900～0.980）。
根据多因素生存模型分析，CXCR1/2表达水平对于无病生存具有独立的预后价值（P=0.003）
CXCR1/2阳性（+）与阴性相比：复发死亡风险高2.149倍（95%置信区间：0.933～4.949）
CXCR1/2阳性（++）与阴性相比：复发死亡风险高3.466倍（95%置信区间：1.569～7.655）
CXCR1/2表达水平较高与较低的患者相比，无病生存比例显著较低（P<0.001）
因此，该研究结果表明，血清CXCL8水平对于三阴性乳腺癌患者的病理完全缓解具有预测价值，术前新辅助化疗后CXCR1/2对于未病理完全缓解患者的无病生存具有预后作用。CXCL8→CXCR1/2可能对于三阴性乳腺癌术前新辅助化疗策略的个体化和调整发挥重要作用，不过还需要开展进一步研究进行验证。
Breast Cancer Res Treat. 2020 May 2. [Epub ahead of print]
Value of CXCL8-CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study.
Ruo-Xi Wang, Peng Ji, Yue Gong, Zhi-Ming Shao, Sheng Chen.
Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Institutes of Biomedical Science, Fudan University, Shanghai, China.
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.
KEYWORDS: Breast cancer, Neoadjuvant chemotherapy, CXCR1, CXCR2, Pathological complete response
DOI: 10.1007/s10549-020-05660-z