Abstract
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.
Similar content being viewed by others
References
Lopez-Bonet E, Alonso-Ruano M, Barraza G, Vazquez-Martin A, Bernado L, Menendez JA (2008) Solid neuroendocrine breast carcinomas: incidence, clinico-pathological features and immunohistochemical profiling. Oncol Rep 20(6):1369–1374
Gunhan-Bilgen I, Zekioglu O, Ustun EE, Memis A, Erhan Y (2003) Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings. Eur Radiol 13(4):788–793. doi:10.1007/s00330-002-1567-z
Hoang MP, Maitra A, Gazdar AF, Albores-Saavedra J (2001) Primary mammary small-cell carcinoma: a molecular analysis of 2 cases. Hum Pathol 32(7):753–757. doi:10.1053/hupa.2001.25603
Papotti M, Macri L, Finzi G, Capella C, Eusebi V, Bussolati G (1989) Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases. Semin Diagn Pathol 6(2):174–188
Miremadi A, Pinder SE, Lee AH, Bell JA, Paish EC, Wencyk P, Elston CW, Nicholson RI, Blamey RW, Robertson JF, Ellis IO (2002) Neuroendocrine differentiation and prognosis in breast adenocarcinoma. Histopathology 40(3):215–222
Righi L, Sapino A, Marchio C, Papotti M, Bussolati G (2010) Neuroendocrine differentiation in breast cancer: established facts and unresolved problems. Semin Diagn Pathol 27(1):69–76
Maluf HM, Koerner FC (1994) Carcinomas of the breast with endocrine differentiation: a review. Virchows Archiv: Int J Pathol 425(5):449–457
Lakhani SEI, Schnitt S et al (2012) WHO classification of tumours of the breast, 4th edn. IARC Press, Lyon
F A Tavassoli, P Devilee (2003) World Health Organization classification of tumours, pathology and genetics of tumours of the breast and female genital organs In: Press I (ed). Lyon, IARC Press, 32–34
Jundt G, Schulz A, Heitz PU, Osborn M (1984) Small cell neuroendocrine (oat cell) carcinoma of the male breast. Immunocytochemical and ultrastructural investigations. Virchows Archiv A, 404 (2):213-221
Wade PM Jr, Mills SE, Read M, Cloud W, Lambert MJ 3rd, Smith RE (1983) Small cell neuroendocrine (oat cell) carcinoma of the breast. Cancer 52(1):121–125
Adams RW, Dyson P, Barthelmes L (2014) Neuroendocrine breast tumours: breast cancer or neuroendocrine cancer presenting in the breast? Breast 23(2):120–127. doi:10.1016/j.breast.2013.11.005
Feyrter F, Hartmann G (1963) On the Carcinoid Growth Form of the Carcinoma Mammae, Especially the Carcinoma Solidum (Gelatinosum) Mammae. Frankfurter Zeitschrift fur Pathologie 73:24–39
Cubilia AL, Woodruff JM (1977) Primary carcinoid tumor of the breast. A report of eight patients. Am J Surg Pathol 1(4):283–292
Lakhani SR, Ellis I, Schnitt S (2012) WHO classification of tumours of the breast. International agency for research on cancer. IARC Press, Lyon
Rovera F, Lavazza M, La Rosa S, Fachinetti A, Chiappa C, Marelli M, Sessa F, Giardina G, Gueli R, Dionigi G, Rausei S, Boni L, Dionigi R (2013) Neuroendocrine breast cancer: retrospective analysis of 96 patients and review of literature. Int J Surg 11(Suppl 1):S79–S83. doi:10.1016/S1743-9191(13)60023-0
Tang F, Wei B, Tian Z, Gilcrease MZ, Huo L, Albarracin CT, Resetkova E, Zhang H, Sahin A, Chen J, Bu H, Abraham S, Wu Y (2011) Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges. Histopathology 59(1):106–115. doi:10.1111/j.1365-2559.2011.03880.x
Sica G, Wagner PL, Altorki N, Port J, Lee PC, Vazquez MF, Saqi A (2008) Immunohistochemical expression of estrogen and progesterone receptors in primary pulmonary neuroendocrine tumors. Arch Pathol Lab Med 132(12):1889–1895. doi:10.1043/1543-2165-132.12.1889
Upalakalin JN, Collins LC, Tawa N, Parangi S (2006) Carcinoid tumors in the breast. Am J Surg 191(6):799–805. doi:10.1016/j.amjsurg.2005.10.021
Tsai WC, Yu JC, Lin CK, Hsieh CT (2005) Primary alveolar-type large cell neuroendocrine carcinoma of the breast. Breast J 11(6):487. doi:10.1111/j.1075-122X.2005.00158.x
Capella C, Eusebi V, Mann B, Azzopardi JG (1980) Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 4(6):613–630
Tsang WY, Chan JK (1996) Endocrine ductal carcinoma in situ (E-DCIS) of the breast: a form of low-grade DCIS with distinctive clinicopathologic and biologic characteristics. Am J Surg Pathol 20(8):921–943
American Cancer Society (2013) Breast Cancer Facts & Figures 2013-2014. American Cancer Society Inc, Atlanta
Kwon SY, Bae YK, Gu MJ, Choi JE, Kang SH, Lee SJ, Kim A, Jung HR, Kang SH, Oh HK, Park JY (2014) Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma. Histopathology 64(5):647–659. doi:10.1111/his.12306
Wei B, Ding T, Xing Y, Wei W, Tian Z, Tang F, Abraham S, Nayeemuddin K, Hunt K, Wu Y (2010) Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma. Cancer 116(19):4463–4473. doi:10.1002/cncr.25352
Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208
Wang J, Wei B, Albarracin CT, Hu J, Abraham SC, Wu Y (2014) Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database. BMC Cancer 14:147. doi:10.1186/1471-2407-14-147
Shin SJ, DeLellis RA, Ying L, Rosen PP (2000) Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol 24(9):1231–1238
Chua RS, Torno RB, Vuletin JC (1997) Fine needle aspiration cytology of small cell neuroendocrine carcinoma of the breast. Acta cytologica 41(4 Suppl):1341–1344
Sebenik M, Nair SG, Hamati HF (1998) Primary small cell anaplastic carcinoma of the breast diagnosed by fine needle aspiration cytology: a case report. Acta Cytol 42(5):1199–1203
Watrowski R, Jager C, Mattern D, Horst C (2012) Neuroendocrine carcinoma of the breast–diagnostic and clinical implications. Anticancer Res 32(11):5079–5082
Saeed A, Rehman A, Zaidi SA, Shaukat T, Jamil K, Abdullah K (2011) Neuroendocrine carcinoma of breast. J Coll Phys Surg Pak: JCPSP 21(6):371–373
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cloyd, J.M., Yang, R.L., Allison, K.H. et al. Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast. Breast Cancer Res Treat 148, 637–644 (2014). https://doi.org/10.1007/s10549-014-3207-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-014-3207-0