Clinical Significance Of Ki-67 On The Efficacy Of Neoadjuvant Chemotherapy For Hormone Receptor Positive HER2 Negative Breast Cancer

Objective Current treatment for breast cancer has entered an era of categorized therapeutic strategies based on the molecular subtypes.The clinical efficacy and outcome varies among different subtypes.In the past,our study shows that achieving pathologic complete response(p CR)after neoadjuvant therapy is of great significance for the choice of subsequent adjuvant therapy and prognosis prediction,especially for HER2 positive and triple negative breast cancer with high recurrence risk,p CR can bring long term survival benefits.However,for hormone receptor positive breast cancer,p CR does not reflect good prognostic value.Ki-67 is an effective index for evaluating the proliferation activity of tumor cells.For hormone receptor positive HER2 negative breast cancer,Studies have shown the correlation between the changes in Ki-67 expression and the recent effect of neoadjuvant endocrine therapy,but few studies have studied its relationship with the therapeutic effect of neoadjuvant chemotherapy and the prognosis.The purpose of this study is to explore the correlation between Ki-67 expression and short-term efficacy and long-term survival benefit in patients with hormone receptor positive HER2 negative breast cancer before and after neoadjuvant chemotherapy,in order to use Ki-67 information screening chemotherapy benefiting people and predicting prognosis.Methods From the neoadjuvant therapy database of breast cancer in our center,we included breast cancer patients with hormone receptor positive and HER2 negative who received neoadjuvant chemotherapy from January 1st 2007 to March 31 st 2017.The expression of Ki-67 and other clinicopathological information were collected before and after neoadjuvant therapy,and the clinical efficacy of neoadjuvant therapy was evaluated by RECIST1.1 solid tumor evaluation criteria.The time from the onset of treatment to the first recurrence or metastasis of breast cancer was followed up.(EFS)The deadline of follow-up was September 30 th 2017.According to the hormone receptor positive breast cancer classification criteria will be defined as the low expression of Ki-67 is less than or equal to 14%,> 14% is defined as high expression.In this study,all patients were treated with neoadjuvant chemotherapy based on anthracycline combined with taxanes,and partial initial anthracycline combined with taxanes regimen with 3 cycles of poor res-ults were replaced by vinorelbine combined with platinum sequential therapy.All patients underwent adjuvant endocrine therapy and were excluded from neoadjuvant endocrine therapy.Using SPSS 20.0 to complete all statistical tests,counting data using paired design ?2 test,using kaplan-meier curve for survival related single factor analysis,using Cox regression model for survival related multifactor analysis.All of them were bilateral test,and the difference was statistically sign-ificant with p<0.05.Results A total of 305 patients with midage 47(26~73)were enrolled in the study,median follow-up time 40(6~90).A total of 290 patients were followed-up and15 patients lost their visits.The rate of missing visits was 4.9%.At the end of follow-up,a total of 67 patients were able to observe terminal events:recurrence or metastasis.1.Analysis of relevant factors affecting the efficacy of neoadjuvant therapy:(1)Clinical efficacy:The clinical effective rate of neoadjuvant therapy in selected pati-ents was 76.4%(233/305).The factors influencing clinical efficacy included age,tumor size,lymph node status,histological grade,Ki-67 express-ion level in primary tumor before neoadjuvant therapy.The results of single factor analysis show that:Patients aged > 45 years,with high Ki-67 expression before treatment,can obtain high chemotherapy efficiency;Multivariate analysis showed that the level of Ki-67 expression before treatment was an independent factor affecting the efficiency of neoadjuvant therapy.(2)p CR:For the 305 cases of hormone receptor positive HER2-negative breast cancer in this study,27 patients were treated with neoadjuvant therapy to reach a p CR,p CR of 8.9%(27/305),There were no statistically significant factors affecting the p CR rate after ?2 test and logistic regression analysis.2.The relationship between the expression of Ki-67 before and after neoadjuvant therapy and survival and prognosis:This study analyzed the correlation between the expression of Ki-67 before and after neoadjuvant therapy and the long-term prognosis.The results showed that the 5-year diseasefree survival rate of patients with high expression of Ki-67 before and after neoadjuvant therapy was lower than that of patients with low expression of Ki-67.(58.9%vs 82.5%,?2=13.964,P < 0.001);The 5-year disease-free survival rate of patients with high expression of Ki-67 after treatment was lower than that of patients with low expression of Ki-67(37.2%vs 84.9%,?2=44.147,P< 0.001).3.The relationship between the change of Ki-67 and survival and prognosis:There were 240 patients with complete information of Ki-67.76.7%(184/240)of these people achieve Ki-67 decrease expression before and after neoadjuvant therapy.The 5-year disease-free survival rate of patients with decreased expression of Ki-67 was higher than that of patients without decreasing expression of Ki-67.(71.7 % vs 55.1 %,P =0.003).According to the high and low Ki-67 before and after treatment,240 patients were divided into 4 groups:a.Low expression group,b.High expression reduced to low ex-pression group,c.Still high expression group,d.No descending group(except low expression).The 5-year disease-free survival rate was better in group a.(90.9%)And group b(80.9%)And group c(18.7%)And d group(19.4%).The prognosis was obviously poor,the overall ?2=33.712,P<0.001.4.Analysis of factors influencing survival and prognosis of patients with ho-rmone receptor positive HER2 negative breast cancer:Univariate analysis showed that no lymph node metastasis and low expression of Ki-67 before or after neoadjuvant therapy were good prognostic factors.However,age,menstrual status,tumor size,clinical efficacy of neoadjuvant therapy and p CR were not significantly correlated with prognosis.Multivariate analysis showed that the presence of lymph node metastasis and the level of Ki-67 expression in tumor residual lesions after neoadjuvant therapy were independent prognostic factors in this subtype.Conclusion1.For hormone receptor positive HER2 negative breast cancer,young,Ki-67 high expression before neoadjuvant treatment of patients,with better neoadjuvant chemotherapy effect;2.The change of Ki-67 expression level after neoadjuvant chemotherapy can provide favorable information for predicting prognosis.After neoadjuvant therapy,the expression of Ki-67 was an independent factor affecting the prognosis of patients.Clinical efficiency of neoadjuvant therapy and p CR were not significantly correlated with the prognosis.