HR+/HER2-乳腺癌患者Ki-67临界值的确定及表达对早期复发转移的影响

Determination of the cut-off value of Ki-67 and its effect on the early recurrence and metastasis in patients with HR+/HER2-breast cancer

目的确定激素受体阳性和人表皮生长因子受体2阴性(HR+/HER2-)乳腺癌患者Ki-67表达高低的临界值,探讨不同Ki-67表达水平对HR+/HER2-乳腺癌早期复发转移的影响。方法回顾性分析我院近5年经手术病理确诊的956例HR+/HER2-乳腺癌患者的病历资料,以中位数作为HR+/HER2-乳腺癌Ki-67表达高低的临界值,分析Ki-67表达水平对HR+/HER2-乳腺癌早期复发转移的影响。结果 956例HR+/HER2-乳腺癌患者Ki-67表达的中位数为20%,5年间Ki-67值分布差异无统计学意义(χ2=16.010,P>0.05)。以20%作为区分Ki-67表达高低的临界值,与国际通用的Ki-67临界值(14%)相比,2种方法判断一致性较好(Kappa值=0.846)。956例患者经4~71个月的随访,共56例出现复发或转移。单因素分析发现,Ki-67表达水平、T分期、N分期、组织学分级、脉管/神经侵犯是HR+/HER2-乳腺癌患者出现早期复发转移的影响因素。多因素分析发现,淋巴结N1~N3分期(HR=2.130,95%CI:1.200~3.781)、Ki-67≥20%(HR=3.271,95%CI:1.441~7.421)是HR+/HER2-乳腺癌无病生存时间(DFS)的独立危险因素。进一步将Ki-67≥20%的患者分层为20%~<30%、30%~<50%和≥50%共3个亚组。与Ki-67<20%患者相比,随着Ki-67表达水平的增高,患者早期复发转移风险比增加(HR分别为2.784、4.409、6.168),5年DFS降低(分别为94.9%、91.3%、87.5%)。结论本中心HR+/HER2-乳腺癌Ki-67表达高低的临界值为20%;随着Ki-67表达水平的增高,患者早期复发转移风险增加,DFS降低。

Objective To determine the cut-off value of Ki-67 expression in hormone receptor positive and human epidermal growth factor receptor 2 negative(HR+/HER2-) breast cancer patients,and to explore the effect of different Ki-67 expression levels on the early recurrence and metastasis of breast cancer.Methods Data of 956 patients with HR+/HER2-breast cancer diagnosed by operation and pathology in our hospital for recent 5 years were retrospectively analyzed.The median was used to determine the cut-off value of Ki-67 expression in HR+/HER2-breast cancer.The effect of Ki-67 expression on the early recurrence and metastasis of HR+/HER2-breast cancer were analyzed.Results The median expression of Ki-67 in 956 patients with HR+/HER2-breast cancer was 20%.There were no significant differences in the shape and position of Ki-67 distribution curve between different years(χ^(2)=16.010,P>0.05).Using 20% as the cut off value for distinguishing the expression of Ki-67,compared with the internationally accepted cut off value of Ki-67(14%),the consistency of the two methods was better(Kappa value=0.846).A total of 956 patients were followed up for 4 to 71 months,and 56 patients had recurrence or metastasis.Univariate analysis showed that Ki-67 expression level,T stage,N stage,histological grade and vascular/nerve invasion were the influencing factors for the early recurrence and metastasis in patients with breast cancer.Multivariate analysis showed that lymph node stage N1-N3(HR=2.130,95%CI:1.200-3.781)and Ki-67≥20%(HR=3.271,95%CI:1.441-7.421) were independent risk factors for disease-free survival(DFS) of HR+/HER2-breast cancer.The patients with Ki-67≥20% will be further divided into 3 subgroups:20%-<30%,30%-<50%and ≥50%.Compared with <20% patients,the risk ratio of the early recurrence and metastasis increased with the increase of Ki-67 expression level(HR=2.784,4.409 and 6.168),and 5-year DFS decreased(94.9%,91.3% and 87.5%).Conclusion The cut-off value of Ki-67 expression in HR+/HER2-breast cancer is 20% in our hospital.With the increase of Ki-67 expression level,the risk ratio of early recurrence and metastasis is increased,DFS is decreased in patients with HR+/HER2-breast cancer.