Significance Of Expression Of Neuroendocrine Markers In Triple-Negative Breast Cancer

BackgroundTriple-negative breast cancer(TNBC)is an aggressive subgroup of breast cancer with heterogeneity in clinical and molecular characteristics,which lacks effective endocrine therapy or targeted therapy.The prognosis of TNBC patients with expression of neuroendocrine(NE)markers hasn't been revealed.The aims of this study were to investigate the incidence of TNBC in breast cancer with expression of NE markers,and to clarify the incidence of expression of NE markers in TNBC and its association with other major clinicopathological parameters,and to determine the prognostic significance of expression of NE markers in patients with TNBC.MethodsClinicopathological data was collected from the patients diagnosed as breast cancer with expression of NE markers(Syn and/or CgA)at Peking Union Medical College Hospital from January 2002 to April 2020.We also collected clinicopathological data from the TNBC patients undergoing radical breast cancer surgery at the same hospital from January 2002 to December 2014,with final follow-up in July 2019.Immunohistochemical staining for NE markers,chromogranin A(CgA)and synaptophysin(Syn)was performed on the samples using tissue microarrays as well as traditional sections.The chi-square or Fisher exact test was used to evaluate the correlations between NE markers(defined as Syn and/or CgA)and patient characteristics.The effects of NE markers and other parameters on disease-free survival(DFS)and overall survival(OS)were accessed using univariate and multivariate analyses.Survival curves were plotted using the Kaplan-Meier method.In addition,the Kappa test was also used to evaluate the consistency of tissue microarrays and traditional sections.ResultsThe data showed that the incidence of TNBC in 490 breast cancer patients with expression of NE markers was 2.7%.The results from traditional sections demonstrated that NE markers were positive in 7.6%of 396 TNBC cases,only 1.0%of which had?50%neoplastic cells expressing NE markers.The expression of any one of two NE markers was associated with negative of basal markers(P=0.004).Kaplan-Meier survival analysis showed that the TNBC patients whose expression rate of NE markers were>1%had a higher disease-free survival rate than those<1%of the same stage(P=0.040).We also found that the expression of Syn had better DFS than the negative group of the same stage(P=0.032).No significant influences of NE markers on DFS and OS were observed in univariate analysis and multivariate analysis.However,multivariate analysis revealed that Syn-positive patients had a lower risk of recurrence compared with Syn-negative patients of the same stage after adjusting for tumor size and Ki-67(P=0.031).In brief,by univariate analysis,age,tumor size,lymph node involvement,stage,and Ki-67 were associated with either DFS or OS.By multivariate analysis,tumor size,stage,and Ki-67 were independent variables associated with either DFS or OS.In addition,the results of Syn and CgA staining on tissue microarrays had poor consistency with those on traditional sections.ConclusionsTNBC patients whose expression rate of NE markers were ? 1%had a better prognosis than those<1%of the same stage.Whether NE markers can be used as biomarkers for predicting the prognosis of TNNBC remains further verification.It is currently not recommended to perform routine NE marker testing for TNBC.