| Objective To analyze the distribution characteristics of HR+/HER2-breast cancer Ki-67 value in Ning Xia Medical University,determine the Ki-67 cut-off value of HR+/HER2-breast cancer to distinguish Luminal A and Luminal B(HER2 negative)breast cancer;To discuss the relationship between the Ki-67 expression at different cut-off values and clinicopathological characteristics and the effect on the early recurrence and metastasis of HR+/HER2-breast cancer.Methods From January 1,2015 to December 31,2019,there are 4532 cases of breast cancer were diagnosed in Ning Xia Medical University,collection of 956 patients with HR+/HER2 breast cancer.The disease-free survival time(DFS)was determined by means of inpatient or outpatient medical records and telephone follow-up visits.The Kruskal-Wallis H test to compare different years the distribution of Ki-67 values,The Ki-67 cut-off value of HR+/HER2-breast cancer was determined by the median.The relationship between Ki-67 expression and clinicopathological characteristics at different cut-off values was analyzed byχ2 test.Kaplan-Meier method was used to draw the survival curve,the Log-rank test analysis different Ki-67 expression level of HR+/HER2-breast cancer early recurrence and metastasis,Cox regression analysis of the effect of Ki-67 expression on the prognosis of HR+/HER2-breast cancer.Results 1.Distribution characteristics of Ki-67 values in HR+/HER2-breast cancer: A total of 956 patients with HR+/HER2-breast cancer from 2015 to 2019 were included in this study.Ki-67 expression ranged from 1%-90%,with a median of 20% and a mean of 25%.Ki-67 expression below 50% accounted for 84.9%(812/956);The median value of Ki-67 was20% in each year,and the mean value of Ki-67 varied in the range of 22%-28%.The shape and position of the distribution curve of Ki-67 values showed no difference among different years(Kruskal-Wallis H test,P=0.103).2.Determination the cut-off value of Ki-67 expression in HR+/HER2-breast cancer: In this study,the median expression of Ki-67 in HR+/HER2-breast cancer was 20%,which could be used as the cut-off value to distinguish between Luminal A and Luminal B(HER2negative)breast cancer.According to the 2011 international breast cancer molecular classification definition(Ki-67 cut off value is 14%)and the results of this study(Ki-67 cut off value is 20%),molecular typing of HR+/ HER2-breast cancer was performed: According to the cut off value of 14%(Ki-67<14% is low expression,Ki-67≥14% is high expression),the low expression of Ki-67 accounted for 33.5%(320/956),were classified as the Luminal A;the high expression of Ki-67 accounted for 66.5%(636/956),were classified as Luminal B(HER2negative);According to the Ki-67 cut off value of 20%(Ki-67<20% is low expression,Ki-67≥20% is high expression),the low expression of Ki-67 accounted for 37.1%(355/956),which was Luminal A.the high expression of Ki-67 was 62.9%(601/956),which was Luminal B(HER2-negative).There was no significant difference between the two groups(χ~2=2.805,P=0.094).3.The Ki-67 expression in different cut off value relationship with clinical pathological features:3.1 The relationship between Ki-67 expression and the clinicopathological characteristics of HR+/ HER2-breast cancer was compared by grouping with 14% and 20% Ki-67 cut off value respectively.The results showed that the histological grade、PR expression、T stage and vascular nerve invasion were all correlated with the Ki-67 expression at different cut off values,the difference was statistically significant(P<0.05).3.2 Among the 956 cases of HR+/HER2-breast cancer,155 cases were classified as grade 1,586 cases as grade 2,and 215 cases as grade 3.The relationship between histological grade and expression of Ki-67 was studied at 20% of the Ki-67,The result found that Ki-67 expression level in different histological grade is different,histologic grade 1 is33.5%(52/155)as high expression of Ki-67,histologic grade 2 is 62.1%(364/586)as high expression of Ki-67,histologic grade 3 is 86%(185/215)as high expression of Ki-67,Ki-67 expression increases with the increase of histological grade,the difference was statistically significant(P < 0.001).4.Influence of Ki-67 expression level on HR+/HER2-early recurrence and metastasis of breast cancer:4.1 956 breast cancer patients were followed up for a median of 37 months(4-77months),during which 56 patients developed recurrence or metastasis,The cut off value of Ki-67 in our hospital was 20%,Ki-67 expression was low in 7 cases,and Ki-67 expression was high in49 cases.including 4 local recurrence,7 regional lymph node metastasis,and 45 distant metastasis.The common distant sites of metastasis were bone,liver and lung,while the rare sites of metastasis were adrenal gland,bone marrow and pericardium.4.2 Single factor Log Rank test showed that Ki-67≥20% patients were more likely to have early recurrence and metastasis,the difference was statistically significant(χ~2=14.89,P=0.0001).Compared with Ki-67<20%,Ki-67≥20% patients had a 4.186 times higher risk of early recurrence and metastasis.The low expression of Ki-67 was significantly higher than the high expression of Ki-67(98% VS 91.8%,P<0.05).Cox regression multivariate analysis showed that Ki-67 was an independent risk factor for HR+/HER2 breast cancer DFS(HR:3.271,95%CI:1.441～7.421,P=0.005).Patients with Ki-67≥20% were divided into three groups: 20%≤ Ki-67<30%,30%≤ Ki-67<50% and Ki-67≥50% to compare the effects of Ki-67 expression in different intervals on HR+/HER2-breast cancer with early recurrence and metastasis.The results showed that: as the Ki-67 expression level increased in patients with early recurrence metastasis than the increased risk(HR: 2.784 VS 4.409VS 6.168),5 years DFS lower(94.9% VS 91.3% VS 87.5%).Conclusions 1.The results of this study suggest that the distribution of Ki-67 value of HR+/HER2-breast cancer in our hospital is consistent and reliable in the past 5 years.The median expression of Ki-67 is 20%,which can be used as the cut off value to distinguish Luminal A and Luminal B(HER2 negative)breast cancer,so as to guide the clinical diagnosis and treatment of breast cancer patients in our hospital.2.Histological grade 、 PR expression 、 T stage and vascular nerve invasion were correlated with the Ki-67 expression.Ki-67 expression was positively correlated with histological grade,suggesting that Ki-67 could predict tumor aggressiveness and histological grade.3.Ki-67 is an independent risk factor for HR+/HER2-breast cancer.Patients with Ki-67≥20% have a high risk of recurrence and a low survival rate.Ki-67 values in different intervals have different effects on the risk of recurrence and metastasis.With the increase of Ki-67 expression level,the risk of recurrence and metastasis increases and DFS decreases. |
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