Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile: a retrospective clinical study

Abstract

BackgroundBreast 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.MethodsWe collected retrospectively patients with NEBC from Oulu and Helsinki University Hospitals in 2007–2015. There were 43 NEBC cases during the period.ResultsThe 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.ConclusionsThere 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.

Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

“…Some very small NEBC series have previously been reported with CD56 expression [19,26]. Higher expression of cytoplasmic CD56 is associated with low proliferation activity of NEBC, which is a typical expression pattern when comparing NEBC to IDC [2].…”

“…NEBC are a rare entity, typically ER-positive and HER2-negative, and frequently resemble luminal A type breast cancers [24]. Nevertheless, NEBC appear to have high locoregional failure rates despite adequate adjuvant therapies [2]. A recent paper with 18 NEBC cases suggested that NEBC have a distinct genetic landscape compared to luminal-type breast cancers, with an enrichment for FOXA1 and TBX3 mutations [25].…”

“…We collected data retrospectively on 53 patients diagnosed with NEBC from Oulu and Helsinki University Hospitals from January 2007 to July 2015, and these characteristics were published previously [2]. A series of 36 of these cases were available for this study ( Table 2).…”

“…We have recently published a study of the largest set of NEBC [2] diagnosed according to the latest WHO criteria [3]. We observed DOI: 10.1159/000493348 that there is a notable difference between the incidence of NEBC in different hospital districts of Finland.…”

“…This is most likely due to different practice for staining neuroendocrine markers, i.e., synaptophysin and chromogranin A. In addition, NEBC patients are, on average, 9 years older than patients with invasive ductal carcinoma (IDC) and NEBC are more aggressive in terms of relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) [2].…”