Study On Prognostic Indicators Of Breast Cancer

Background and objective:Trastuzumab-based therapy is a standard,targeted treatment for HER2-positive breast cancer in the adjuvant setting.However,patients do not benefit equally from it and the association between HER2 amplification level and patients'survival remains controversial.A systematic review and meta-analysis was conducted by incorporating all available evidence to evaluate the association between disease free survival(DFS)and HER2 amplification level.Methods:Databases including PubMed,Embase,Web of Science,and Cochrane Central Register of Controlled Trials(CENTRAL),were searched for eligible literature.HER2 amplification level was evaluated by fluorescence in situ hybridization(FISH)in terms of gene copy number(GCN)and HER2/CEP17 ratio.Hazard ratios(HRs)for DFS with 95%confidence interval(CI)according to the amplification level of HER2 were extracted.The outcomes were synthesized based on a fixed-effects model.Results:Three cohort studies involving 1360 HER2-positive breast cancer patients stratified by HER2 amplification magnitude were eligible for meta-analysis.The combined HRs for DFS were 1.05(95%CI:0.80-1.36,p = 0.74)and 0.97(95%CI:0.73-1.29,p = 0.83)for HER2 gene copy number(GCN)and HER2/CEP 17 ratio.No evidence of heterogeneity or public bias was found.Conclusions:HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based targeted therapy in the clinical adjuvant setting.Estrogen receptor signalling plays important regulatory roles in multiple mammalian physiological processes.Dysregulation of estrogen receptor(ER)expression and/or its associated signaling pathway is strongly associated with the development,progression,transition,and endocrine-resistance of breast cancer.Non-coding transcripts are essential regulators of almost every level of gene regulation.However,few long non-coding RNAs(lncRNAs)associated with the estrogen receptor signaling pathway have been well-described.We used array-based methods to identify 33 estrogen receptor agitation-related(ERAR)lncRNAs.A coding-non-coding gene co-expression network analysis suggested that 15 ERAR lncRNAs were associated with mitosis,DNA damage,and DNA repair.Kaplan-Meier analysis indicated that five ERAR IncRNAs selected using the Random Forest-Recursive Feature Elimination algorithm were significantly correlated with endocrine resistance-free survival and distant metastasis-free survival as well as disease free survival.Our results suggest that ERAR lncRNAs may serve as novel biomarkers for guiding breast cancer treatment and prognosis.Furthermore,our findings reveal a new avenue by which estrogen receptor signalling can be further explored.Purpose:The incidence of breast cancer is increasing,and the triple-negative breast cancer(TNBC)has least treatments and worst prognosis.TTK is a key kinase in cell cycle,and it is over-expressed in breast cancer especially TNBC.TTK inhibitors decrease the viability and tumorgenicity of TNBC cells and make tumor cells more sensitive to antimicirotubular agents.TTK may be an important biomarker in oncogenesis and treatment of TNBC.It is unclear whether TTK expression level is related with TNBC prognosis.This study was intended to explore the prognostic significance of TTK expression in primary TNBC.Methods:The research objects are TNBC cases.Tumor tissue samples and clinical-pathological information of 169 cases without preoperation treatment were collected.TTK expression was tested by immunohistochemistry(IHC).A receiver operating characteristic(ROC)curve was used to identify a cutpoint for TTK expression.Chi-square test,log-rank test,and Cox regression analysis were used to analyze the association between TTK expression level and cases' clinicopathological factors and survival.Results:169 TNBC cases were included.All cases had integrated clinical-pathological baseline information,immunihistochemistry results and follow-up information,excepting five cases lost follow-up.The immunohistochemistry results showed that TTK was cytoplasm/membrane positive in 99.4%(1/169)of cases,while nucleus positive in 5.9%(10/169)of cases.The cutoff value of TTK expression calculated with ROC curve was 55(H-score),and high-expression was defined as more than 55,and low-expression was defined as less than 55.Chi-square test showed that TTK level was related with molecular subgroup of TNBC,but not other conventional clinical-pathological factors.Log-rank univariable survival analysis showed that lymph vascular invasion(LVI),tumor size,number of positive lymph nodes,pathological stage,chemotherapy regimen,and TTK expression level were associated with DFS,and lymph vascular invasion(LVI),number of positive lymph nodes,pathological stage,chemotherapy regimen,radiotherapy and TTK expression level were associated with OS.Elevated TTK expression was associated with prolonged disease free survival(DFS)(p<0.001)and overall survival(OS)(p=0.024)in primary TNBC.In addition,Cox regression analysis demonstrated that TTK expression was an independent prognostic factor for DFS in TNBC(p<0.001).TTK expression level also display prognostic value in subgroup analysis.Conclusions:H-score 55 could be regarded as a cutoff value for TTK expression in immunohistochemistry experiment;TTK expression has no relationship with traditional clinical-pathological factors except molecular subgroup;TTK is a prognostic biomarker for TNBC survival-high expression level indicating better prognosis and low expression level relating with worse prognosis.