Correlation Analysis Of Clinical Biological Indicators With Efficacy And Prognosis Of Neoadjuvant Chemotherapy In Breast Cancer

Background:Breast cancer is a very common malignant tumors,causing great harm to women’s life and health.With the continuous advance of medical technology,the trerapy of breast cancer has also changed from surgical resection to systemic comprehensive treatment based on operation.Neoadjuvant chemotherapy(NAC),an important adjuvant therapy can provide some inoperable patients with the opportunity of surgery,and even enable some patients to obtain the possibility of breast conservation,and has been increasingly used in locally advanced breast cancer.However,there are still some patients who cannot benefit from NAC,or even delay the disease.Objective:To explore the relationship between different clinical features as well as biological indicators and the efficacy of NAC,and to analyze the changes and significance of biological indicators before and after NAC,thereby providing some basis for guiding NAC in breast cancer patients.Methods:We collected the clinical data of female breast cancer patients treated with neoadjuvant chemotherapy in Qilu Hospital of Shandong University from April 2015 to August 2019,including general conditions,clinical features,treatment options and pathological results.The chi-square test or Fisher’s exact test was used to carry out univariate analysis of the relationship between various clinical characteristics as well as biological indicators and the efficacy of NAC.The correlation between the continuous data and the efficacy of NAC was obtained by drawing the ROC curve,and obtaimed the cutoff value.Binary Logistic regression was used to conduct multivariate analysis of the relationship between each index and the efficacy of NAC,and to obtain independent factors affecting the efficacy of NAC.Paired chi-square test or Wilcoxon signed-rank test was used to analyze the changes and significance of clinical biological indicators before and after NAC.The Kappa consistency test was used to analyze the correlation between the pathological evaluation and clinical evaluation system of NAC.KM survival analysis,Log-rank test and COX proportional hazards regressionwere used in univariate analysis and multivariate analysis of prognosis and obtained the independent factors that affect the prognosis.Results:1.A total of 160 patients were included into the cohort and follow up were completed.In this cohort,16(10%)patients achieved pCR,and 13(8.1%)patients achieved clinical complete remission(cCR).Univariate analysis of the effect of NAC showed:the clinical stage(p=0.038),histological grade(p=0.007),ER(p=0.004),(PR)(p=0.003),Ki-67 expression(p<0.001)and luminal type(p=0.005)of patients before NAC were the influencing factors of PCR,and the cutoff value of Ki-67 for predicting pCR was 57.5%.Histological grade(p=0.023)and PR(p=0.028)before NAC were the influencing factors of CCR.Multivariate analysis showed that clinical stage was an independent predictor of pCR in breast cancer(OR=0.243,95%CI:0.063-0.948,P=0.042),and patients with clinical stage Ⅱ were more easily to obtain pCR.2.The expression of Ki-67 in patients after NAC was significantly decreased(P<0.001).The correlation analysis showed that the degree of Ki-67 decreased was not significantly correlated with the Miller-Payne(MP)classification(P=0.632)and RECIST standard(P=0.367)of NAC efficacy.However,The expression of ER,PR,HER-2 and p53 showed no obvious discrepancy before and after NAC(P>0.05).3.Kappa consistency test was performed on the pathological evaluation system MP classification and the clinical evaluation system RECIST standard of NAC efficacy,and it was found that MP classification and RECIST standard were consistent in the evaluation of NAC efficacy(Kappa value=0.225,P<0.001),but the consistency is not high,so clinical evaluation cannot completely replace pathological evaluation.4.Univariate analysis of the prognosis of patients showed:family history of breast cancer(P=0.012),age(P=0.045),Ki-67 expression level before NAC(P=0.044),degree of clinical remission(P=0.015)and lymph node metastasis(P=0.002)are significantly correlated with DFS.Histological grade before NAC(P=0.036),and ER before NAC(P=0.007),Luminal type after NAC(P=0.014),ER after NAC(P=0.001),Ki-67 expression level after NAC(P=0.005)correlated with OS.Multivariate analysis showed that the lymph node metastasis(P=0.007)and the degree of clinical remission after NAC(P=0.026)were independent factors affecting the DFS of NAC patients,and the expression of Ki-67 after NAC(P=0.042)is the independent factors affecting the OS of NAC patients.Conclusion:1.Patients with ER negative,PR negative,high Ki-67 expression,clinical stage Ⅱ,histopathological grade 3 and non-Luminal type before NAC have better NAC efficacy,the cutoff value of Ki-67 for predicting pCR is 57.50%,and the clinical stage before NAC can independently predict pCR.2.NAC can reduce the expression of Ki-67 in patients,but the decreased degree of Ki-67 can not represent the efficacy of NAC.3.There is consistency between clinical evaluation and pathological evaluation of NAC,but the consistency is low,and clinical evaluation cannot completely replace pathological evaluation.4.Patients with family history of breast cancer,age ≤ 35 years old,high expression of Ki-67 before NAC,progressive disease(PD)after NAC and axillary lymph node metastasis>5 have poor DFS,progressive disease(PD)after NAC and axillary lymph node metastasis>5 are independent factors affecting DFS in NAC patients.5.Patients with negative ER,grade 3 histopathology before NAC and ER negative,high expression of Ki-67 and non-Luminal type after NAC have poor OS,and high expression of Ki-67 after NAC is an independent factor affecting the OS of NAC patients.