全身免疫炎症指数与三阴性乳腺癌新辅助化疗疗效及预后的相关性

Association between systemic immune-inflammation index and neoadjuvant chemotherapy efficacy as well as prognosis in triple-negative breast cancer

目的:三阴性乳腺癌(triple-negative breast cancer,TNBC)是一种高度侵袭性的乳腺癌亚型,预后相对较差。新辅助化疗(neoadjuvant chemotherapy,NAC)是TNBC的主要治疗手段,但由于肿瘤的异质性,TNBC患者对化疗的反应存在显著差异。炎症与癌症的发生和发展息息相关,全身免疫炎症指数(systemic immune-inflammation index,SII)是一项全面反映机体炎症状态的指标。本研究旨在探讨SII与NAC治疗TNBC疗效及预后的相关性。方法:收集2015年1月至2019年6月在中南大学湘雅医院接受NAC和系统治疗的TNBC患者资料,依据纳入和排除标准,最终纳入231例TNBC患者。根据患者化疗前1周的血常规结果计算NAC前SII,将患者分为NAC前低SII组(SII<412,115例)和NAC前高SII组(SII≥412,116例)。根据患者所有化疗结束后2~3个月的血常规结果计算化疗后SII,将患者分为化疗后低SII组(SII<474,115例)和化疗后高SII组(SII≥474,116例)。采用Pearson’sχ^(2)检验分析TNBC患者SII与其他临床特征的关系以及TNBC患者NAC疗效与临床特征的关系;采用二元logistic回归分析TNBC患者NAC疗效的独立影响因素;采用Kaplan-Meier曲线分析影响TNBC患者预后的因素;采用Cox回归模型分析TNBC患者预后的独立影响因素。结果:在NAC前,不同年龄、肿块大小组之间SII的差异均有统计学意义(分别P=0.007和P=0.002);在化疗后,不同年龄、肿块大小、组织学分级、淋巴结分期、Ki-67组之间SII的差异均无统计学意义(均P>0.05)。NAC前低SII组病理完全缓解(pathological complete response,pCR)率为15.7%,NAC前高SII组pCR率为6.0%。NAC前低SII组较NAC前高SII组pCR率更高(P=0.019)。淋巴结分期为pN_(0)的患者156例,pCR率为14.7%;淋巴结分期为pN_(1)~pN_(2)的患者75例,pCR率为2.7%。淋巴结分期为pN_(0)的患者较淋巴结分期为pN_(1)~pN_(2)的患者pCR率更高(P=0.006)。随访期间有34例患者发生局部复发或远处转移。Kaplan-Meier生存曲线显示:NAC前低SII、NAC前高SII患者的3年无病生存(disease-free survival,DFS)率分别为87.8%、82.8%,前者明显高于后者(P=0.005);肿块大小为T_(1)~T_(2)、T_(3)患者的3年DFS率分别为89.0%、67.5%,前者明显高于后者(P=0.001);淋巴结分期为pN_(0)、pN_(1)~pN_(2)患者的3年DFS率分别为87.8%、82.8%,前者明显高于后者(P=0.009)。Cox分析结果显示:NAC前SII和肿块大小是患者DFS的独立影响因素(分别P=0.038和P=0.010)。结论:SII对预测TNBC患者NAC疗效及预后具有重要的临床意义,具有成为生物学标志物的潜力。

Objective: Triple-negative breast cancer(TNBC) is a highly aggressive subtype of breast cancer with a relatively poor prognosis. Neoadjuvant chemotherapy(NAC) is the main treatment method. Due to the heterogeneity of the tumor, the chemotherapy response of TNBC patients is significantly different. Inflammation is closely related to the occurrence and development of cancer. The systemic immune-inflammation index(SII) is an indicator that can comprehensively reflect the state of systemic inflammation. This study aims to explore the association between SII and the NAC efficacy as well as the prognosis in TNBC.Methods: The data of TNBC patients who underwent NAC and systemic treatment in Xiangya Hospital of Central South University from January 2015 to June 2019 were collected. According to the inclusion and exclusion criteria, 231 TNBC patients were finally included. The pre-NAC SII was calculated according to the blood routine results of the patients at 1 week before chemotherapy, and the patients were divided into a pre-NAC low SII group(SII<412, 115 cases) and a pre-NAC high SII group(SII≥412, 116 cases).The SII after chemotherapy was calculated according to the blood routine results of the patients at 2 to 3 months after the end of chemotherapy, and the patients were divided into a low SII group after chemotherapy(SII<474, 115 cases) and a high SII group after chemotherapy(SII≥474, 116 cases). Pearson’ s chi-square test was used to analyze the relationship between SII and other clinical characteristics of TNBC patients, and the relationship between the NAC efficacy and clinical characteristics of TNBC patients. Binary logistic regression analysis was used to find independent factors that affect the efficacy of NAC in TNBC patients. Kaplan-Meier curve analysis was used to analyze factors affecting the prognosis of TNBC patients. Cox regression model was used to find independent factors affecting the prognosis of TNBC patients.Results: Before NAC, the differences in SII between groups with different ages and tumor sizes were significant(P=0.007 and P=0.002, respectively);after chemotherapy, there were no significant differences in SII between different ages, tumor sizes, histological grades,lymph node staging, and Ki-67 groups(all P>0.05). There were 115 patients with low SII before NAC, with a pathological complete response(p CR) rate of 15.7%;there were 116 patients with high SII before NAC, with a p CR rate of 6.0%. Patients with low SII before NAC had a higher p CR rate than patients with high SII before NAC, and the difference was statistically significant(P=0.019). There were 156 patients with lymph node staging pN0,with a p CR rate of 14.7%;and there were 75 patients with lymph node staging pN1-pN2,with a p CR rate of 2.7%. Patients with lymph node staging pN0 had a higher p CR rate than those with lymph node staging pN1-pN2, and the difference was significant(P=0.006).During the follow-up, 34 patients had local recurrence or distant metastasis. The KaplanMeier survival curve showed that the 3-year disease-free survival(DFS) rates for patients with low SII before NAC and high SII before NAC were 87.8% and 82.8%, respectively,and the former was significantly higher than the latter(P=0.005);the 3-year DFS rates for patients with tumor sizes of T1-T2 and T3 were 89.0% and 67.5%, respectively, and the former was significantly higher than the latter(P=0.001);the 3-year DFS rates for patients with lymph node staging of pN0 and pN1-pN2 were 87.8% and 82.8%, respectively, and the former was significantly higher than the latter(P=0.009). Cox analysis showed that SII before NAC and tumor size were independent influencing factors of patients’ DFS(P=0.038, P=0.010, respectively).Conclusion: SII has important clinical significance in predicting the efficacy and prognosis of NAC in TNBC patients, and it has the potential to be a biomarker.