title: Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile: a retrospective clinical study.
abstract: Breast carcinomas with neuroendocrine features (NEBC) are a very rare entity of mammary neoplasms, WHO classification of which has recently been revised. There are very limited data available about the clinical behaviour and treatment options of NEBC.
  
  
  
  We collected retrospectively patients with NEBC from Oulu and Helsinki University Hospitals in 2007-2015. There were 43 NEBC cases during the period.
  
  
  
  The incidence of NEBC from all breast cancers varied from 0.1% in Helsinki to 1.3% in Oulu. The mean tumor size was 2.2 cm and 23 patients (55.8%) had no lymph node metastases when diagnosed. In total, 4 patients (9.3%) had distant metastases at the time of diagnosis. High estrogen receptor (ER) expression was observed in 41 (97.7%) patients. When non-metastatic NEBC were compared to a prospective set of ductal carcinomas (n = 506), NEBC were more often HER2 negative (p = 0.046), ER positive (p = 0.0062) and the NEBC patients were older (p < 0.0005) than patients with ductal carcinomas. Plasma chromogranin A correlated only to higher age at diagnosis (p = 0.0028). Relapse-free survival (p = 0.0013), disease-free survival (p = 0.024) and overall survival (p = 0.0028) favoured ductal carcinomas compared to NEBC, while no difference was observed in distant disease-free survival or in breast cancer-specific survival.
  
  
  
  There is remarkable variation in the incidence of NEBC in Finland, which is likely to be explained by differences in the use of neuroendocrine marker immunostainings. Poor local control and worse overall survival may be linked to the more aggressive biology of the disease, despite its association with apparently indolent prognostic factors.
authors.affiliation: Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 22, FIN-90029, Oulu, Finland.|Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Nelli
authors.initials: N
authors.lastname: Roininen
authors.affiliation: Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Takala
authors.affiliation: Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 22, FIN-90029, Oulu, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
authors.affiliation: Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mattson
authors.affiliation: Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.affiliation: Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 22, FIN-90029, Oulu, Finland. peeter.karihtala@oulu.fi.
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Incidence; Neuroendocrine carcinoma; Prognosis; World Health Organization