HER2表达水平对三阴性乳腺癌新辅助化疗疗效及预后的影响

Effect of HER2 expression on the curative effect and prognosis of neoadjuvant chemotherapy for triple negative breast cancer

目的探讨人表皮生长因子受体2(HER2)表达水平(0、1+、2+且FISH无扩增)对三阴性乳腺癌(TNBC)患者新辅助化疗(NAC)疗效的影响以及预后价值。方法回顾性分析郑州大学附属肿瘤医院2014-01-01-2018-12-31接受NAC治疗的221例TNBC患者临床病理资料,并通过门诊就诊系统进行随访。采用双侧χ^(2)检验分析临床资料与HER2的相关性。二元Logistic回归分析临床病理因素对病理完全缓解(PCR)的影响。不同临床病理亚组与无病生存(DFS)率的生存分析采用Kaplan-Meier曲线描述,并行Log-Rank检验。影响预后的因素采用Cox回归分析。结果221例患者中,70例(31.67%)在NAC后达到PCR状态。随访1~73个月,中位随访时间23个月,共66例(29.86%)患者出现了复发或转移。单因素分析显示,与PCR相关的因素是临床T分期(χ^(2)=10.410,P=0.005)和HER2表达水平(χ^(2)=6.181,P=0.045)。进一步行多因素二元Logistic回归分析,PCR的独立影响因素是临床T分期(OR=0.454,95%CI为0.246~0.839,P=0.012)与HER2表达水平(OR=0.605,95%CI为0.413~0.884,P=0.010)。Kaplan-Meier生存分析结果显示,HER2表达水平(χ^(2)=42.34,P<0.001)、术后淋巴结分期(χ^(2)=49.62,P<0.001)均与DFS呈负关联,PCR比非PCR的DFS率高,χ^(2)=27.19,P<0.001。多因素Cox回归分析显示,DFS的独立预后因素是PCR(HR=2.832,95%CI为1.139~7.040,P=0.025)、HER2表达水平(HR=2.132,95%CI为1.571~2.894,P<0.001)以及术后淋巴结分期(HR=1.509,95%CI为1.190~1.913,P=0.001)。结论在TNBC患者中,HER2表达水平是患者预后重要预测指标,其表达水平越低,NAC后越容易达到PCR,预后结果越好。

Objective To investigate the effect of expression levels(0,1+,2+)of human epidermal growth factor receptor 2(HER2)on the efficacy of neoadjuvant chemotherapy(NAC)and its prognostic value in patients with triple negative breast cancer(TNBC).Methods A total of 221 patients with TNBC treated with NAC who were admitted to the Affiliated Tumor Hospital of Zhengzhou University from January 2014 to December 2018 were included in the retrospective study.The correlation between clinical data and HER2 was analyzed by bilateral chi-square test.Binary Logistic regression was used to analyze the effects of clinical pathological factors on pathologic complete response(PCR).Survival analyses for different clinicopathologic subgroups and disease-free survival(DFS)rates were described by the K-M curve and performed in parallel with the Log-Rank test.Factors affecting prognosis were analyzed by Cox regression analysis.Results Of the 221 patients,31.67%(70 patients)achieved PCR status after NAC.The median follow-up time was 23 months,ranging from 1 to 73 months,and a total of 29.86%(66 patients)experienced recurrence or metastasis.Univariate analysis showed that the PCR-associated factors were clinical T stage(χ^(2)=10.410,P=0.005)and HER2 expression level(χ^(2)=6.181,P=0.045).Further multivariate binary Logistic regression analyses revealed that independent influencing factors of PCR were clinical T stage(OR=0.454,95%CI:0.246-0.839,P=0.012)and HER2 expression level(OR=0.605,95%CI:0.413-0.884,P=0.010).K-M survival analyses showed that both HER2 expression level(χ^(2)=42.34,P<0.001)and postoperative lymph node stage(χ^(2)=49.62,P<0.001)were negatively correlated with DFS,and DFS rate of PCR was higher than that of non-PCR(χ^(2)=27.19,P<0.001).Multivariate Cox regression analyses illustrated that the independent prognostic factors for DFS were PCR(HR=2.832,95%CI:1.139-7.040,P=0.025),HER2 expression level(HR=2.132,95%CI:1.571-2.894,P<0.001),and postoperative lymph node stage(HR=1.509,95%CI:1.190-1.913,P=0.001).Conclusions The expression level of HER2 is an important predictor of prognosis in TNBC patients.The lower the expression level is,the easier it is to achieve PCR after NAC,and the better the prognosis can obtain.