A Retrospective Study On The Expression Of Proliferative And Invasive Genes-Related Protein And Its Value Of Prognosis In ER/PR-Positive And HER2-Negative Breast Cancer

Objective: Breast cancer is one of the most common cancers in women.According to the latest China city report data 2017,breast cancer has become the main burden of urban female cancer,mainly because of female pressure,late marriage and late childbirth,fast pace of life.As a curable disease,it will be a valuable treatment strategy and research direction if breast cancer has been early diagnosed by looking for effective prognostic and predictive markers to improve the 5-year survival rate of patients with breast cancer.Studies on breast cancer proliferative and invasive genes help to judge the prognosis of patients,and provide powerful basis for comprehensive treatment of breast cancer.According to ASCO and NCCN guidelines in 2007 and 2008,patients whose ER/PR are positive and have nagative axillary lymph node with early breast cancer should take21 genetic testing.St Gallen expert consensus meeting pointed out in 2011: Hormone receptor-positive,her2-negative breast cancer molecular classification of patients need to distinguish Luminal A or Luminal type B by the percentage of Ki67(14%),and even decide whether these two kinds of patients need cytotoxic therapy on the basis of endocrine therapy.In these years,clinical doctors judge these patients whether need to add chemotherapy according to Ki67.However,may use Ki67 index only is reliable,whether should we add some new proliferation of breast cancer gene protein expression detection as screening indicators to replace 21 genetic testing? It is not clear.Therefore,we made a retrospective study on the expression of proliferative and invasive genes-related protein and its value of prognosis in ER/PR-positive and HER2-negative breast cancer.Methods: This study selected 390 cases whose ER/PR are positive and Her2 are negative from the First Affiliated Hospital of China Medical University with breast cancer from May 2010 to December 2013.The expression of proliferative and invasive protein in breast cancer(Ki-67,STK15,Survivin,CyclinB1,MYBL2,Stromelysin3,CathepsinL2)in these cases were detected by immunohistochemical analysis on paraffin specimen microarray.Analyse the experimental result and form a rating system(7-protein rating)including the above genes.Design the control group which only detects the Ki-67,a common used marker in molecular subtyping to decide whether to useadjuvant chemotherapy or not in hormone receptor-positive and Her-2 negative breast cancer.Results: 1.Proliferative and invasive genes express in breast cancer specimens.Ki-67 and MYBL2 were located mainly in the nucleus,Survivin,CyclinB1,Cathepsin L2,STK15 were located mainly in the cytoplasm,and Stromelysin3 was secreted.2.Relevance to clinical pathological factors: The statistical analysis shows that the expression of Ki67 associated with histological grade significantly(P=0.004),and had no significant correlation with age,menstrual status,tumor size,axillary lymph node metastasis.The expression of 7-Protein in breast cancer associated with histological grade(P < 0.001),tumor size(P = 0.018),axillary lymph node(P = 0.008),respectively,significantly.3.Among the 390 cases,according to the follow-up data,a total of 356 patients survive and overall survival rate is 91.3%.The Kaplan Meier survival curve analysis that the expression of these proteins is negatively related to the survival rate.The Log-rank test shows that the two groups of low and high expression of Ki67 have no significant differences in survival curves(P = 0.208).Through the 7-Protein score,patients in high risk group showed significantly less favorable survival rates compared with patients in low risk group(P=0.002).4.The patients receiving chemotherapy in7-Protein group(96%)have favorable survival rates than those who haven't received chemotherapy(86%),however,the patients in ki67 group(92%)have no significant difference with those who haven't received chemotherapy(90%).Conclusions: Compared with the use of Ki67,breast cancer proliferation and invasive genes related protein expression levels(7-Protein score)can reflect more tumor biology dangerous levels;7-Protein score can reflect the prognosis of patients with tumor;7-Protein score as a judge index for the chemotherapy might be more accurate,more easily to find benefit group of patients,which could help achieve precise treatment,and avoid excessive chemotherapy.