乳腺癌新辅助全身治疗后病理完全缓解的预测因子:一项单中心回顾性研究

Predictors of pathological complete response after neoadjuvant therapy in breast cancer:a single-center retrospective study

目的探讨乳腺癌患者新辅助全身治疗(NST)后病理完全缓解(pCR)的预测因子。方法回顾性分析2016年1月1日至2021年3月1日在陆军军医大学大坪医院行空芯针穿刺活组织检查诊断为乳腺浸润性癌,并且接受NST后行手术切除的516例患者临床病理资料,包括患者年龄、月经状态、临床分期、NST方案及周期、组织学类型、组织学分级、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型及术后Miller-Payne(MP)病理评级(G1、G2、G3、G4、G5)。pCR被定义为G5并且区域淋巴结阴性。采用Kruskal-Wallis H检验分析不同临床病理特征组间MP病理评级,采用χ^(2)检验分析不同临床病理特征组间pCR率的差异。采用单因素和逐步向前Logistic回归模型分析pCR的独立预测因素。结果(1)MP病理评级:G4~G5(病理缓解组)123例(23.8%),G1~G3(病理未缓解组)393例(76.2%)。患者临床分期、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型、NST方案、NST周期均与MP评级有关(χ^(2)=13.572、19.687、18.963、17.989、15.493、27.605、31.622、10.103,P均<0.050)。pCR 59例(11.4%),非pCR 457例(88.6%)。患者月经状态、组织学分级、ER表达、PR表达、HER-2表达、Ki-67表达、分子分型、NST方案、NST周期均与pCR有关(χ^(2)=3.898、9.854、30.593、17.582、20.611、9.303、33.286、34.546、13.846,P均<0.050)。(2)各分子分型间病理缓解率的差异有统计学意义(χ^(2)=42.117,P<0.001)。(3)多因素Logistic回归分析显示:绝经前患者、临床Ⅲ~Ⅳ期、组织学分级为3级、NST方案含有靶向药物、HER-2阳性型和basal-like型是pCR率增高的独立预测因素(OR=0.475,95%CI:0.256~0.881,P=0.018;OR=0.487,95%CI:0.238~0.998,P=0.049;OR=2.108,95%CI:1.073~4.141,P=0.030;OR=5.576,95%CI:1.958~15.874,P=0.001;OR=10.128,95%CI:1.076~95.312,P=0.043;OR=18.497,95%CI:2.254~151.815,P=0.007)。(4)临床Ⅲ~Ⅳ期、NST方案含有靶向药物、NST周期≥5个周期、luminal B(HER-2阴性)型、luminal B(HER-2阳性)型、HER-2阳性型和basallike型是病理缓解率增高的独立预测因素(OR=0.436,95%CI:0.258~0.738,P=0.002;OR=2.305,95%CI:1.109~4.792,P=0.025;OR=2.718,95%CI:1.121~6.588,P=0.027;OR=6.764,95%CI:1.950~23.463,P=0.003;OR=8.094,95%CI:2.048~31.989,P=0.003;OR=12.125,95%CI:3.097~47.460,P<0.001;OR=17.182,95%CI:4.874~60.577,P<0.001)。结论luminal B(HER-2阳性)型、HER-2阳性型及basal-like型(较之于luminal A型)、临床分期早、组织学分级高、ER和PR阴性、HER2阳性、Ki-67高表达、NST周期≥5个及采用了靶向治疗的患者具有较高的pCR率;而月经状态、临床分期、组织学分级、分子分型及NST方案是pCR的独立预测因子。

Objective To investigate the predictors of pathological complete response(pCR)after neoadjuvant systemic therapy(NST)in breast cancer patients.Methods The clinicopathological data of 516 patients with invasive breast cancer who underwent core needle biopsy and surgical resection after NST in the Daping Hospital,Army Medical University from January 1,2016 to March 1,2021 were retrospectively analyzed,including patient age,menstrual status,clinical stage,NST regimen and cycle,histological type,histological grade,ER expression,PR expression,HER-2 expression,Ki-67 expression,molecular subtype and postoperative Miller-Payne grades(G1,G2,G3,G4,G5).pCR was defined as G5 with negative regional lymph nodes.The Kruskal-Wallis H test was used to compare the Miller-Payne grades among patients with different clinicopathological characteristics,andχ^(2) test was used to compare the pCR rates.Univariate and forward stepwise logistic regression models were used to analyze independent predictors of pCR.Results(1)According to the Miller-Payne grades,there were 123 cases(23.8%)of G4-G5(pathological remission group),and 393 cases(76.2%)of G1-G3(non-pathological remission group).Clinical stage,ER expression,PR expression,HER-2 expression,Ki-67 expression,molecular subtypes,NST regimen and NST cycle were all related to the patients’Miller-Payne grades(χ^(2)=13.572,19.687,18.963,17.989,15.493,27.605,31.622,10.103,all P<0.050).There were 59 cases(11.4%)of pCR and 457 cases(88.6%)of non-pCR.Menstrual status,histological grade,ER expression,PR expression,HER-2 expression,Ki-67 expression,molecular subtypes,NST regimen,and NST cycle were all related to the patients’pCR(χ^(2)=3.898,9.854,30.593,17.582,20.611,9.303,33.286,34.546,13.846,all P<0.050).(2)The pathological remission rate showed a significant difference among molecular subtypes(χ^(2)=42.117,P<0.001).(3)The logistic regression analysis showed that premenopausal status,clinical stageⅢ-Ⅳ,histological grade 3,targeted drugs in NST regimen,HER-2 positive subtype and basal-like subtype were independent predictive factors of increased pCR rate(OR=0.475,95%CI:0.256-0.881,P=0.018;OR=0.487,95%CI:0.238-0.998,P=0.049;OR=2.108,95%CI:1.073-4.141,P=0.030;OR=5.576,95%CI:1.958-15.874,P=0.001;OR=10.128,95%CI:1.076-95.312,P=0.043;OR=18.497,95%CI:2.254-151.815,P=0.007).(4)Clinical stageⅢ-Ⅳ,targeted drugs in NST regimen,NST cycles≥5,luminal B(HER-2 negative)subtype,luminal B(HER-2 positive)subtype,HER-2 positive subtype and basal-like subtype were independent predictive factors of increased pathological remission rate(OR=0.436,95%CI:0.258-0.738,P=0.002;OR=2.305,95%CI:1.109-4.792,P=0.025;OR=2.718,95%CI:1.121-6.588,P=0.027;OR=6.764,95%CI:1.950-23.463,P=0.003;OR=8.094,95%CI:2.048-31.989,P=0.003;OR=12.125,95%CI:3.097-47.460,P<0.001;OR=17.182,95%CI:4.874-60.577,P<0.001).Conclusions The patients with luminal B(HER-2 positive),HER-2 positive and basallike subtypes(compared with luminal A subtype),early clinical stage,advanced histological grade,ER and PR negative,HER-2 positive,high Ki-67 expression,NST cycles≥5 and targeted therapy have higher pCR rates.Menstrual status,clinical stage,histological grade,molecular subtype and NST regimen were independent predictors of pCR.