Medical Oncology

, Volume 29, Issue 4, pp 2613–2618 | Cite as

Primary neuroendocrine breast cancer, how much do we know so far?

Review Article

Abstract

Primary neuroendocrine cancer of the breast (NECB) is an extremely rare tumor. In 2003, the World Health Organization (WHO) recognized this category with three well-described subtypes: small cell, large cell, and carcinoid-like carcinoma; very few peer-review publications based on the WHO definition were encountered in the literature, and we conducted a literature search to investigate the reported incidence, diagnosis, prognosis, hormone receptor status, and treatment options for this rare tumor. Confirming the breast as an origin of neuroendocrine tumor represents a challenge. The diagnosis is mainly dependent on the exclusion of other extra-mammary organs based on clinical, radiological, and pathological data. Except for the very rare type small cell carcinoma, estrogen and progesterone receptors were reported to be expressed in 90 and 83 % of NECB, respectively. It is hypothesized that primary breast neuroendocrine carcinoma differentiates from the epithelial cells during the carcinogenesis process; the prognosis of non-small cell primary NECB seems to improve as the amount of mucinous component increases in the tumor specimen. Management similar to interventions utilized to manage the usual ductal-type carcinoma has been attempted in the past, such as chemotherapy and hormonal therapy; however, due to the rarity of the tumor, none of the published studies are randomized nor do they have a large number of patients. Additionally, none of reports analyzed NECB based on its distinct subtypes. These limitations make recommendations largely based on anecdotal and small observatory studies and call for the need for further research in this extremely rare tumor.

Keywords

Breast cancer Neuroendocrine cancer Treatment Pathology Prognosis Management 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Cubilla AL, Woodruff JM. Primary carcinoid tumor of the breast. A report of eight patients. Am J Surg Pathol. 1977;1:283–92.CrossRefGoogle Scholar
  2. 2.
    Azzopardi JG, Muretto P, Goddeeris P, Eusebi V, Lauweryns JM. Carcinoid tumors of the breast: the morphological spectrum of argyrophil carcinomas. Histopathology. 1982;6:549–69.PubMedCrossRefGoogle Scholar
  3. 3.
    Papotti M, Macri L, Finzi G, Capella C, Eusebi V, Bussolati G. Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases. Semin Diagn Pathol. 1989;6:174–88.PubMedGoogle Scholar
  4. 4.
    Sapino A, Righi L, Cassoni P, Papotti M, Pietribiasi F, Bussolati G. Expression of the neuroendocrine phenotype in carcinomas of the breast. Semin Diagn Pathol. 2000;17:127–37.PubMedGoogle Scholar
  5. 5.
    Sapino A, Bussolati G. Is detection of endocrine cells in breast adenocarcinoma of diagnostic and clinical significance? Histopathology. 2002;40:211–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Ellis P, Schnitt SJ, Sastre-Garau X. Invasive breast carcinoma. In: Tavassoli FA, Deyilee P, editors. Tumors of the Breast and Female Genital Organ: Pathology and Genetics. Lyon: France, IARC Press; 2003.Google Scholar
  7. 7.
    Makretsov N, Gilks CB, Coldman AJ, Hayes M, Huntsman D. Tissue microarray analysis of neuroendocrine differentiation and its prognostic significance in breast cancer. Hum Pathol. 2003;34:1001–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Miremadi A, Pinder SE, Lee AH, Bell JA, Paish EC, Wencyk P, Elston CW, Nicholson RI, Blamey RW, Robertson JF, Ellis IO. Neuroendocrine differentiation and prognosis in breast adenocarcinoma. Histopathology. 2002;40:215–22.PubMedCrossRefGoogle Scholar
  9. 9.
    van Krimpen C, Elferink A, Broodman CA, Hop WC, Pronk A, Menke M. The prognostic influence of neuroendocrine differentiation in breast cancer: results of a long-term follow-up study. Breast. 2004;13:329–33.PubMedCrossRefGoogle Scholar
  10. 10.
    Lopez-Bonet E, Alonso-Ruano M, Barraza G, Vazquez-Martin A, Bernado L, Menendez JA. Solid neuroendocrine breast carcinomas: Incidence, clinico-pathological features and immunohistochemical profiling. Oncol Rep. 2008;20:1369–74.PubMedGoogle Scholar
  11. 11.
    Gunhan-Bilgen I, Zekioglu O, Ustun EE, Memis A, Erhan Y. Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings. Eur Radiol. 2003;13:788–93.PubMedGoogle Scholar
  12. 12.
    Wei B, Ding T, Xing Y, Wei W, Tian Z, Tang F, Abraham S, Nayeemuddin K, Hunt K, Wu Y. Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma. Cancer. 2010;116:4463–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Richter-Ehrenstein C, Arndt J, Buckendahl AC, Eucker J, Weichert W, Kasajima A, Schneider A, Noske A. Solid neuroendocrine carcinomas of the breast: metastases or primary tumors? Breast Cancer Res Treat. 2010;124:413–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Rovera F, Masciocchi P, Coglitore A, La Rosa S, Dionigi G, Marelli M, Boni L, Dionigi R. Neuroendocrine carcinomas of the breast. Int J Surg. 2008;6(Suppl 1):S113–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Zekioglu O, Erhan Y, Ciris M, Bayramoglu H. Neuroendocrine differentiated carcinomas of the breast: a distinct entity. Breast. 2003;12:251–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Righi L, Sapino A, Marchio C, Papotti M, Bussolati G. Neuroendocrine differentiation in breast cancer: established facts and unresolved problems. Semin Diagn Pathol. 2010;27:69–76.PubMedCrossRefGoogle Scholar
  17. 17.
    Maluf HM, Koerner FC. Carcinomas of the breast with endocrine differentiation: a review. Virchows Arch. 1994;425:449–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Moriya T, Kanomata N, Kozuka Y, Fukumoto M, Iwachido N, Hata S, Takahashi Y, Miura H, Ishida K, Watanabe M. Usefulness of immunohistochemistry for differential diagnosis between benign and malignant breast lesions. Breast Cancer. 2009;16:173–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Capella C, Usellini L, Papotti M, Macri L, Finzi G, Eusebi V, Bussolati G. Ultrastructural features of neuroendocrine differentiated carcinomas of the breast. Ultrastruct Pathol. 1990;14:321–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Kiriakogiani-Psaropoulou P, Malamou-Mitsi V, Martinopoulou U, Legaki S, Tamvakis N, Vrettou E, Fountzilas G, Skarlos D, Kosmidis P, Pavlidis N. The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study. Lung Cancer. 1994;11:353–64.PubMedCrossRefGoogle Scholar
  21. 21.
    Adegbola T, Connolly CE, Mortimer G. Small cell neuroendocrine carcinoma of the breast: a report of three cases and review of the literature. J Clin Pathol. 2005;58:775–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Shin SJ, DeLellis RA, Ying L, Rosen PP. Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol. 2000;24:1231–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Volante M, Righi, Asioli S, et al.: Goblet cell carcinoids and other mixed neuroendocrine/non neuroendocrine neoplasms. Virchows Arch 451:S51–S69, 2007 (suppl 1).Google Scholar
  24. 24.
    Sapino A, Righi L, Cassoni P, Papotti M, Gugliotta P, Bussolati G. Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women. Mod Pathol. 2001;14:768–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Tse GM, Tan PH, Lau KM, et al. Breast cancer in the elderly: a histological assessment. Histopathology. 2009;55:441–51.PubMedCrossRefGoogle Scholar
  26. 26.
    Upalakalin JN, Collins L, Tawa N, Parangi S. Carcinoid tumors in the breast. Am J Surg. 2006;191:799–805.PubMedCrossRefGoogle Scholar
  27. 27.
    Fujimoto Y, Yagyu R, Murase K, Kawajiri H, Ohtani H, Arimoto Y, Yamamura T, Inoue T, Moritani S. A case of solid neuroendocrine carcinoma of the breast in a 40-year-old woman. Breast Cancer. 2007;14:250–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Adams RF, Parulekar V, Hughes C, Kadour MJ, Talbot D. Radiologic characteristics and management of screen-detected metastatic carcinoid tumor of the breast: a case report. Clin Breast Cancer. 2009;9:189–92.PubMedCrossRefGoogle Scholar
  29. 29.
    Landon G, Sneige N, Ordonez NG, Mackay B. Carcinoid metastatic to breast diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol. 1987;3:230–3.PubMedCrossRefGoogle Scholar
  30. 30.
    Hoang MP, Maitra A, Gazdar AF, Albores-Saavedra J. Primary mammary small-cell carcinoma: a molecular analysis of 2 cases. Hum Pathol. 2001;32:753–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Sica G, Wagner P, Altorki N, Port J, et al. Immunohistochemical expression of estrogen and progesterone receptors in primary pulmonary neuroendocrine tumors. Arch Pathol Lab Med. 2008;132:1889–95.PubMedGoogle Scholar
  32. 32.
    Clark JW, Snell L, Shiu RP, Orr FW, Maitre N, Vary CP, Cole DJ, Watson PH. The potential role for prolactin-inducible protein (pip) as a marker of human breast cancer micrometastasis. Br J Cancer. 1999;81:1002–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Shin SJ, DeLellis RA, Rosen PP. Small cell carcinoma of the breast–additional immunohistochemical studies. Am J Surg Pathol. 2001;25:831–2.PubMedCrossRefGoogle Scholar
  34. 34.
    Chan JK, Suster S, Wenig BM, Tsang WY, Chan JB, Lau AL. Cytokeratin 20 immunoreactivity distinguishes merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites. Am J Surg Pathol. 1997;21:226–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Eyden B, Banerjee SS, Nesland JM. Amphicrine carcinoma of breast with giant granules: an immunohistochemical, histochemical and ultrastructural study. J Submicrosc Cytol Pathol. 2002;34:27–36.PubMedGoogle Scholar
  36. 36.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRefGoogle Scholar
  37. 37.
    Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.PubMedCrossRefGoogle Scholar
  38. 38.
    Tian Z, Wei B, Tang F, Wei W, Gilcrease MZ, Huo L, Albarracin CT, Resetkova E, Middleton L, Sahin A, Xing Y, Hunt KK, Chen J, Bu H, Rashid A, Abraham SC, Wu Y. Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation. Hum Pathol. 2011;42:1169–77.PubMedCrossRefGoogle Scholar
  39. 39.
    Diab SG, Clark GM, Osborne CK, Libby A, Allred DC, Elledge RM. Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol. 1999;17:1442–8.PubMedGoogle Scholar
  40. 40.
    Pagani A, Sapino A, Eusebi V, Bergnolo P, Bussolati G. Pip/gcdfp-15 gene expression and apocrine differentiation in carcinomas of the breast. Virchows Arch. 1994;425:459–65.PubMedCrossRefGoogle Scholar
  41. 41.
    Hahnel R, Hahnel E. Expression of the pip/gcdfp-15 gene and survival in breast cancer. Virchows Arch. 1996;429:365–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Bigotti G, Coli A, Butti A, del Vecchio M, Tartaglione R, Massi G. Primary small cell neuroendocrine carcinoma of the breast. J Exp Clin Cancer Res. 2004;23:691–6.PubMedGoogle Scholar
  43. 43.
    Latif N, Rosa M, Samian L, Rana F. An unusual case of primary small cell neuroendocrine carcinoma of the breast. Breast J. 2010;16:647–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Buttar A, Mittal K, Khan A, Bathini V. Effective role of hormonal therapy in metastatic primary neuroendocrine breast carcinoma. Clin Breast Cancer. 2011;11:342–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the united states. J Clin Oncol. 2008;26:3063–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Homam Alkaied
    • 1
  • Kassem Harris
    • 1
  • Basem Azab
    • 1
  • Qun Dai
    • 1
  1. 1.Staten Island University HospitalStaten IslandUSA

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