Analysis Of Prognostic Factors Of Breast Neuroendocrine Neoplasm Based On SEER Database

Objective:Primary breast neuroendocrine neoplasma is a rare breast tumor,its incidence is low,and it is difficult to diagnose.The incidence of neuroendocrine neoplasm may be underestimated due to the fact that immunohistochemistry is neither routine nor recommended.At present,most of the studies on breast neuroendocrine neoplasm are case reports and small sample studies.Therefore,we analyzed the clinicopathological characteristics and prognostic factors of patients with breast neuroendocrine neoplasm(Br-NEN)based on SEER(surveillance,epidemiology,and end results)database to help clinicians judge the prognosis.Methods:Clinical and pathological data of patients with pathologically diagnosis of Br-NEN from 2012 to 2016 was collected retrospectively by SEER*stat software.The ICD-O3 anatomical codes included c50.0-c50.6,c50.8-c50.9,except breast skin c44.5.The 2012 WHO breast tumor classifification system was utilized for categorizing and abstracting NECB cases based on the following histopathology: well differentiated neuroendocrine tumor,NOS(8246/3),poorly differentiated or small cell/oat cell neuroendocrine carcinoma(8041/3-8045/3),adenocarcinoma with neuroendocrine characteristics(8574/3),malignant carcinoid(8240/3),large cell neuroendocrine carcinoma(8013/3).Patients with other tumors and male patients were excluded.When analyzing the difference of clinicopathological data in different histological types,chi square test was used for disordered classification variables,and rank sum test was used for ordered classification variables.Kaplan Meier method was used for survival analysis and cancer specific survival(CSS)rate was calculated.Log rank test was used for survival rate comparison.Multivariate Cox regression model was created to evaluate factors associated with CSS of Br-NEN patients.The difference was statistically significant with P <0.05.Results:A total of 260 patients with pathologic diagnosed as Br-NEN in SEER database were screened out.67 patients with other tumors were excluded,and then 1 male was excluded.192 patients were finally included in the analysis.The 1-year,3-year and 4-year cumulative survival rates was 83.85%,78.65% and 77.60%,respectively.Large cell carcinoma was combined with malignant carcinoid.Patients were divided into 4groups,including small cell carcinoma,NEC-NOS,adenocarcinoma with NE,large cell carcinoma and carcinoid.The most common types of small cell carcinoma were ER negative/unknown,PR negative/unknown and triple negative.The other three groups were mainly ER positive,PR positive and luminal A type.The PR positive group and negative / unknown group of NOS-Br NEN both accounted for about 50%respectively,but the positive group accounted for 51.9%.The proportion of patients without operation/unknown was the highest in small cell carcinoma,while the proportion of patients with surgery was the highest in patients of large cell carcinoma and malignant carcinoid.The proportion of well and moderately differentiated type,poorly differentiated type,and undifferentiated type in NEC-NOS was 42%,56.8%,1.1%,respectively.The proportion in adenocarcinoma with NE was 48.6%,45.9%,5.4%,respectively.The degree of differentiation of SCC was worse than that of the above two types(7.4%,81.5%and 11.1%),P=0.000(NOS-NEC)and P=0.001(adenocarcinoma with NE).But we can’t concluded that SCC was the one with the worst differentiation because it can not be confirmed that the differe-ntiation of SCC was worse than that of large cell and carcinoid(P>0.05).Univariate analysis showed that age,tumor location,tumor size,grade,stage,ER status,PR status,radiotherapy,surgery or not and even operation types were the prognostic factors of Br-NEN(P<0.05).Multivariate Cox analysis showed that age,grade,stage,ER status,radioathrapy and operation were independent factors that affecting the prognosis of Br-NEN.Compared with patients younger than 69 years old at the time of diagnosis,patients older than 69 was signifificantly associated with worse CSS(HR=4.153,95%CI:1.98-8.71,P=0.000).Compared with well and moderately differentiation,poorly differentiation(HR=4.851,95%CI: 1.292-18.208,P=0.019)and undifferentiation(HR=11.347,95%CI:1.840-69.960,P=0.009)were obviously associated with worse CSS.Compared with patients of AJCC stage I,prognosis of patients of stage IV was worse(HR=9.540,95%CI:1.598-56.971,P=0.013).Compared with patients with negative ER status/unknown,HR of patients with positive ER status is 0.167,95%CI: 0.045-0.619,P=0.007.Compared with patients without radiotherapy/unknown,HR of patients with radiation therapy is 0.451(95%CI:0.205-0.993,P=0.048).Compared with patients without surgery/unknown,HR of patients with surgery is 0.352(95%CI:0.141-0.879,P=0.025).The 1-year,3-year,4-year CSS of patients with surgery was 94.07%(127/135),90.37%(122/135),88.89%(120/135),respectively.While 1-year,3-year,4-year CSS of patients without surgery was 59.65%(34/57),50.88%(29/57),50.88%(29/57),respectively.Conclusion:Primary breast neuroendocrine neoplasm is a rare type of breast tumor.Most of the small cell carcinomas are ER negative/unknown,PR negative/unknown and triple negative.The degree of differentiation of SCC is worse than that NEC-NOS and adenocarcinoma with NE.ER positive,PR positive and luminal A type were more common in the rest three types.The PR positive group and negative / unknown group of NOS-Br NEN both accounted for about 50% respectively,but the positive group accounted for 51.9%.Age≥69 years old at the time of diagnosis,high grade and AJCC stage IV may be risk factors for the prognosis of patients with Br-NEN.ER positive,radiotherapy and primary site surgery may be protective factors for the prognosis of patients,which is helpful to judge the prognosis of patients.Patients with Br-NEN should strive for radiotherapy and surgery when conditions permit.