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

OBJECTIVES: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC. METHODS: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC). RESULTS: Nuclear and cytoplasmic TS, nuclear and cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was associated with excellent distant disease-free survival (p = 0.013), cytoplasmic menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27 with longer breast cancer-specific survival (p = 0.022). CONCLUSIONS: There is a striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and NEBC also appear to show similar expression patterns of the studied markers, while there are notable differences compared to IDC. Due to the wide expression of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be evaluated.

Metaplastic carcinoma of the breast: Prognosis and response to systemic treatment in metastatic disease.

BACKGROUND: Metaplastic breast carcinomas (MpBCs) are rare, aggressive breast cancers. Due to the scant literature of this disease most guidelines do not give recommendation for this entity. The aim of the study was to review the clinicopathologic features, treatment, and outcomes of the patients with MpBC treated at our institution. MATERIAL AND METHODS: We searched databases for patients with histologically confirmed MpBC from 2002 to 2016. RESULTS: A total of 78 patients with MpBC were included in the study. All histological material was reviewed by an experienced breast pathologist. Most tumors were grade 3 (83%) and triple negative (85%). Eighty-two percent were node negative. Sixty-four percent received adjuvant chemotherapy. The 5-year disease free survival was 63% and 5-year breast cancer specific overall survival was 61%. Tumor size and mixed metaplastic histology were associated with worse outcome in this patient group. One third of the patients (n = 28) had metastatic disease at initial presentation or developed metastases at follow-up. The lungs were the most common site of first distant recurrence. Half (n = 14) of these patients received palliative chemotherapy. Of those only 6% (n = 2) had partial response and 18% had stable disease as best response to treatment. The median overall survival time with metastatic disease was only 3.4 months. CONCLUSION: MpBC is an aggressive type of breast cancer with poor outcome despite low nodal involvement and aggressive local and systemic therapy. Tumor response to palliative systemic chemotherapy remains poor for MpBC patients.

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

BACKGROUND: 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. METHODS: We collected retrospectively patients with NEBC from Oulu and Helsinki University Hospitals in 2007-2015. There were 43 NEBC cases during the period. RESULTS: 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. CONCLUSIONS: 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.