Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast

Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an increasingly recognized entity. The current literature is limited to case reports and small series and therefore a comprehensive population-based analysis was conducted to investigate the clinicopathologic features and long-term outcomes associated with NECB. We included all patients in the SEER Database from 2003 to 2010 with a diagnosis of NECB. The 2012 WHO classification system was used to categorize patients based on histopathologic diagnosis: well-differentiated neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine tumors, adenocarcinoma with neuroendocrine features (ANF), large cell neuroendocrine and carcinoid tumors. Survival analysis was performed for disease specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1 % were classified as well-differentiated, 25.7 % small cell, 14.8 % ANF, 4.9 % large cell, and 2.5 % carcinoid. In general, patients presented with advanced disease: 36.2 % had positive lymph node metastases and 20.4 % presented with systemic metastases. Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4 %, respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9 %, respectively. DSS and OS were significantly different for well-differentiated neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On univariate Cox proportional hazards regression, small cell carcinoma was significantly associated with worse DSS (OR 1.97, 95 % CI 1.05-3.67) and OS (OR 2.66, 95 % CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is associated with advanced stage disease at presentation and an unfavorable prognosis for stage II-IV disease and small cell, large cell, and carcinoid histologic subtypes.