Breast Cancer Research and Treatment

, Volume 148, Issue 3, pp 637–644 | Cite as

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

  • Jordan M. Cloyd
  • Rachel L. Yang
  • Kimberly H. Allison
  • Jeffrey A. Norton
  • Tina Hernandez-Boussard
  • Irene L. Wapnir


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.


Breast cancer Neuroendocrine tumors Carcinoid Small cell carcinoma World Health Organization Lumpectomy Mastectomy SEER program 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    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):1369–1374PubMedGoogle Scholar
  2. 2.
    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 PubMedGoogle Scholar
  3. 3.
    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 PubMedCrossRefGoogle Scholar
  4. 4.
    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):174–188PubMedGoogle Scholar
  5. 5.
    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):215–222PubMedCrossRefGoogle Scholar
  6. 6.
    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):69–76PubMedCrossRefGoogle Scholar
  7. 7.
    Maluf HM, Koerner FC (1994) Carcinomas of the breast with endocrine differentiation: a review. Virchows Archiv: Int J Pathol 425(5):449–457CrossRefGoogle Scholar
  8. 8.
    Lakhani SEI, Schnitt S et al (2012) WHO classification of tumours of the breast, 4th edn. IARC Press, LyonGoogle Scholar
  9. 9.
    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, 32–34Google Scholar
  10. 10.
    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):213-221Google Scholar
  11. 11.
    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):121–125PubMedCrossRefGoogle Scholar
  12. 12.
    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 PubMedCrossRefGoogle Scholar
  13. 13.
    Feyrter F, Hartmann G (1963) On the Carcinoid Growth Form of the Carcinoma Mammae, Especially the Carcinoma Solidum (Gelatinosum) Mammae. Frankfurter Zeitschrift fur Pathologie 73:24–39PubMedGoogle Scholar
  14. 14.
    Cubilia AL, Woodruff JM (1977) Primary carcinoid tumor of the breast. A report of eight patients. Am J Surg Pathol 1(4):283–292CrossRefGoogle Scholar
  15. 15.
    Lakhani SR, Ellis I, Schnitt S (2012) WHO classification of tumours of the breast. International agency for research on cancer. IARC Press, LyonGoogle Scholar
  16. 16.
    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 PubMedCrossRefGoogle Scholar
  17. 17.
    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 PubMedCrossRefGoogle Scholar
  18. 18.
    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 PubMedGoogle Scholar
  19. 19.
    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 PubMedCrossRefGoogle Scholar
  20. 20.
    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 PubMedCrossRefGoogle Scholar
  21. 21.
    Capella C, Eusebi V, Mann B, Azzopardi JG (1980) Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 4(6):613–630PubMedCrossRefGoogle Scholar
  22. 22.
    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):921–943PubMedCrossRefGoogle Scholar
  23. 23.
    American Cancer Society (2013) Breast Cancer Facts & Figures 2013-2014. American Cancer Society Inc, AtlantaGoogle Scholar
  24. 24.
    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 PubMedCrossRefGoogle Scholar
  25. 25.
    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 PubMedCrossRefGoogle Scholar
  26. 26.
    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 PubMedCrossRefGoogle Scholar
  27. 27.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    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):1231–1238PubMedCrossRefGoogle Scholar
  29. 29.
    Chua RS, Torno RB, Vuletin JC (1997) Fine needle aspiration cytology of small cell neuroendocrine carcinoma of the breast. Acta cytologica 41(4 Suppl):1341–1344PubMedCrossRefGoogle Scholar
  30. 30.
    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):1199–1203PubMedCrossRefGoogle Scholar
  31. 31.
    Watrowski R, Jager C, Mattern D, Horst C (2012) Neuroendocrine carcinoma of the breast–diagnostic and clinical implications. Anticancer Res 32(11):5079–5082PubMedGoogle Scholar
  32. 32.
    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):371–373Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jordan M. Cloyd
    • 1
  • Rachel L. Yang
    • 1
  • Kimberly H. Allison
    • 2
  • Jeffrey A. Norton
    • 1
  • Tina Hernandez-Boussard
    • 1
  • Irene L. Wapnir
    • 1
  1. 1.Departments of SurgeryStanford UniversityStanfordUSA
  2. 2.Departments of PathologyStanford UniversityStanfordUSA

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