Prediction of Metastasis and Recurrence of Breast Carcinoma: Detection of Survivin-Expressing Circulating Cancer Cells

  • Shang-mian Yie
Part of the Methods of Cancer Diagnosis, Therapy and Prognosis book series (HAYAT, volume 1)

Breast cancer is the most common type of cancer for women in the world. According to Bray et al. (2004), it is responsible for over one million of the estimated ten million neoplasms diagnosed worldwide each year. Globally, it is also the leading cause of cancer deaths among women, responsible for 375,000 deaths in the year 2000 as documented by Ferlay et al. (2001). Major causes for these breast cancer-related deaths, as indicated by Zieglschmid et al. (2005) have been metastases and recurrences. As a result, the ability to predict an individual patient’s risk of metastasis and recurrence after surgical resection of the primary tumor is of great importance. This ability would also allow for the planning of optimized adjuvant therapies as well as monitoring the efficacy of treatments.


Breast Cancer Breast Cancer Cell Reverse Transcriptase Polymerase Chain Reaction Circulate Tumor Cell Survivin Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adida, C., Crotty, P.L., McGrath, J., Berrebi, D., Diebold, J., and Altieri, D.C. 1998. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am. J. Pathol. 152: 43–49PubMedGoogle Scholar
  2. Aerts, J., Wynendaele, W., Paridaens, R., Christiaens M.R., van den Bogaert, W., van Oosterom, A.T., and Vandekerckhove, F. 2001. A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood. Ann. Oncol. 12: 39–46PubMedCrossRefGoogle Scholar
  3. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison S.J., and Clarke, M.F. 2003. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA. 100: 3983–3988PubMedCrossRefGoogle Scholar
  4. Ambrosini, G., Adida, C., and Altieri, D.C. 1997. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat. Med. 3: 917–921PubMedCrossRefGoogle Scholar
  5. Bosma, A.J., Weigelt, B., Lambrechts, A.C., Verhagen, O.J., Pruntel, R., Hart, A.A., Rodenhuis, S., and van't Veer, L.J. 2002. Detection of circulating breast tumor cells by differential expression of marker genes. Clin. Cancer Res. 8: 1871–1877PubMedGoogle Scholar
  6. Bray, F., McCarron, P., and Parkin, M.D. 2004. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 6: 229–239PubMedCrossRefGoogle Scholar
  7. Chiou, S.K., Jones, M.K., and Tarnawski, A.S. 2003. Survivin—an anti-apoptosis protein: its biological roles and implications for cancer and beyond. Med. Sci. Monit. 9: 125–129Google Scholar
  8. Cianfrocca, M., and Goldstein, L.J. 2004. Prognostic and predictive factors in early stage breast cancer. Oncologist 9: 606–616PubMedCrossRefGoogle Scholar
  9. Denley, H., Pinder, S.E., Elston, C.W., Lee, A.H.S., and Ellis, I.O. 2002. Preoperative assessment of prognostic factors in breast cancer. J. Clin. Pathol. 54: 20–24CrossRefGoogle Scholar
  10. Ferlay, J., Bray, F., Pisani, P., and Parkin, D.M. 2001. GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, IARC Cancer Base No. 5. Lyon: IARC PressGoogle Scholar
  11. Fisher, B., Jeong, J.H., Anderson, S., Bryant, J., Fisher, E.R., and Wolmark, N. 2002. Twenty-five year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. New Engl. J. Med. 347: 567–575PubMedCrossRefGoogle Scholar
  12. Gilbey, A.M., Burnett, D., Coleman, R.E., and Holen, I. 2004. The detection of circulating breast cancer cells. J. Clin. Pathol. 57: 903–911PubMedCrossRefGoogle Scholar
  13. Goeminne, J.C., Guillaume, T., Salmon, M., Machiels, J.P., D'Hondt, V., and Symann, M. 1999. Unreliability of carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain reaction (RT-PCR) in detecting contaminating breast cancer cells in peripheral blood stem cells due to induction of CEA by growth factors. Bone Marrow Transplant 24: 769–775PubMedCrossRefGoogle Scholar
  14. Gross, H.J., Verwer, B., Houck, D., Hoffman, R.A., and Recktenwald, D. 1995. Model study detecting breast cancer cells in peripheral blood mononuclear cells at frequencies as low as 10−7. Proc. Natl. Acad. Sci. USA. 92: 537–541PubMedCrossRefGoogle Scholar
  15. Konno, R., Yamakawa, H., Utsunomiya, H., Ito, K., Sato, S., and Yajima, A. 2000. Expression of survivin and Bcl-2 in the normal human endometrium. Mol. Hum. Reprod. 6: 529–534PubMedCrossRefGoogle Scholar
  16. Johnson, M.E., and Howerth, E.W. 2004. Survivin: a bifunctional inhibitor of apoptosis protein. Vet. Pathol. 41: 599–607PubMedCrossRefGoogle Scholar
  17. Jung, R., Kruger, W., Hosch, S., Holweg, M., Kroger, N., Gutensohn, K., Wagener, C., Neumaier, M., and Zander, A.R. 1998. Specificity of reverse transcriptase polymerase chain reaction assays designed for the detection of circulating cancer cells is influenced by cytokines in vivo and in vitro. Br. J. Cancer 78: 1194–1198PubMedGoogle Scholar
  18. Lacroix, M. 2006. Significance, detection and markers of disseminated breast cancer cells. Endoc.-Relat. Cancer 13: 1033–1067CrossRefGoogle Scholar
  19. Lambrechts, A.C., Bosma, A.J., Klaver, S.G., Top, B., Perebolte, L., van't Veer, L.J., and Rodenhuis, S. 1999. Comparison of immuno-cytochemistry, reverse transcriptase polymerase chain reaction, and nucleic acid sequence-based amplification for the detection of circulating breast cancer cells. Breast Cancer Res. Treat. 56: 219–231PubMedCrossRefGoogle Scholar
  20. Li, F., and Brattain, M.G. 2006. Role of the survivin gene in pathophysiology. Am. J. Pathol. 169: 1–11PubMedCrossRefGoogle Scholar
  21. Manhani, A.R., Manhani, R., Soares, H.P., Bendit, I., Lopes, F., Nicoletti, A.G. Fonseca, F.L., Novaes, M., Zatta, S.M., Arias, V. , Giralt, S., and del Giglio, A. 2001. CK-19 expression by RT-PCR in the peripheral blood of breast cancer patients correlates with response to chemotherapy. Breast Cancer Res. Treat. 66: 249–254PubMedCrossRefGoogle Scholar
  22. Mehes, G., Witt, A., Kubista, E., and Ambros, P.F. 2001. Circulating breast cancer cells are frequently apoptotic. Am. J. Pathol. 159: 17–20PubMedGoogle Scholar
  23. Mirza, A.N., Mirza, N.O., Vlastos, G., and Singletary, S.E. 2002. Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann. Surg. 235: 10–26PubMedCrossRefGoogle Scholar
  24. Muller, V., and Pantel, K. 2004. Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives. Breast Cancer Res. 6: 258–261PubMedCrossRefGoogle Scholar
  25. Nasu, S., Yagihashi, A., Izawa, A., Saito, K., Asanuma, K., Nakamura, M., Kobayashi, D., Okazaki, M., and Watanabe, N. 2002. Survivin mRNA expression in patients with breast cancer. Anticancer Res. 22: 1839–1843PubMedGoogle Scholar
  26. Pachmann, K., Heiss, P., Demel, U., and Tilz, G. 2001. Detection and quantification of small numbers of circulating tumor cells in peripheral blood using laser scanning cytometer (LSC). Clin. Chem. Lab. Med. 39: 811–817PubMedCrossRefGoogle Scholar
  27. Pantel, K., and Brakenhoff, R.H. 2004. Dissecting the metastatic cascade. Nat. Rev. Cancer 4: 448–456PubMedCrossRefGoogle Scholar
  28. Pizzoferrato, E., Liu, Y., Gambotto, A., Armstrong, M.J., Stang, M.T., Gooding, W.E., Alber, S.M., Shand, S.H., Watkins, S.C., Storkus, W.J., and Yim, J.H. 2004. Ectopic expression of interferon regulatory factor-1 promotes human breast cancer cell death and results in reduced expression of survivin. Cancer Res. 64: 8381–8388PubMedCrossRefGoogle Scholar
  29. Ring, A., Smith, I.E., and Dowsett, M. 2004. Circulating tumor cells in breast cancer. Lancet Oncol. 5: 79–88PubMedCrossRefGoogle Scholar
  30. Ryan, B., O'Donovan, N., Browne, B., O'Shea, C., Crown, J., Hill, A.D., McDermott, E., O'Higgins, N ., and Duffy, M.J. 2005. Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer. Br. J. Cancer 92: 120–124PubMedCrossRefGoogle Scholar
  31. Smith, B.M., Slade, M.J., English, J., Graham, H., Luchtenborg, M., Sinnett, H.D., Cross, N.C., and Coombes, R.C. 2000. Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemi-cal techniques. J. Clin. Oncol. 18: 1432–1439PubMedGoogle Scholar
  32. Span, P.N., Sweep, F.C., Wiegerinck, E.T., Tjan-Heijnen, V.C., Manders, P., Beex, L.V., and de Kok, J.B. 2004. Survivin is an independent prognostic marker for risk stratification of breast cancer patients. Clin. Chem. 50: 1986–1993PubMedCrossRefGoogle Scholar
  33. Span, P.N., Tjan-Heijnen, V.C., Heuvel, J.J., de Kok, J.B., Foekens, J.A., and Sweep, F.C. 2006. Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer? Clin. Chem. 52: 1693–1700PubMedCrossRefGoogle Scholar
  34. Stathopoulou, A., Vlachonikolis, I., Mavroudis, D., Perraki, M., Kouroussis, C., Apostolaki, S., Malamos, N., Kakolyris, S., Kotsakis, A., Xenidis, N., Reppa, D., and Georgoulias, V. 2002. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: valuation of their prognostic significance. J. Clin. Oncol. 20: 3404–3412PubMedCrossRefGoogle Scholar
  35. Taback, B., Chan, A.D., Kuo, C.T., Bostick, P.J., Wang, H.J., Giuliano, A.E., and Hoon, D.S. 2001. Detection of occult metastatic breast cancer cells in blood by a multimolecular marker assay: correlation with clinical stage of disease. Cancer Res. 61: 8845–8850PubMedGoogle Scholar
  36. Valasek, M.A., and Repa, J.J. 2005. The power of realtime PCR. Advan. Physiol. Educ. 29: 151–159CrossRefGoogle Scholar
  37. Yie, S.M., Luo, B., Ye, N.Y., Xie, K., and Ye, S.R. 2006. Detection of Survivin expressing circulating cancer cells in the peripheral blood of breast cancer patients by a RT-PCR ELISA. Clin. Exp. Metastasis 23: 279–289PubMedCrossRefGoogle Scholar
  38. Zach, O., Kasparu, H., Wagner, H., Krieger, O., and Lutz, D. 2002. Prognostic value of tumour cell detection in peripheral blood of breast cancer patients. Acta. Med. Austriaca 29 [Suppl 59]: 32–34Google Scholar
  39. Zaffaroni, N. and Daidone, M.G. 2002. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist. Updates 5: 65–72CrossRefGoogle Scholar
  40. Zaffaroni, N., Pennati, M., and Daidone, M.G. 2005. Survivin as a target for new anticancer interventions. J. Cell. Mol. Med. 9: 360–372PubMedCrossRefGoogle Scholar
  41. Zieglschmid, V., Hollmann, C., and Bocher, O. 2005. Detection of disseminated tumor cells in peripheral blood. Crit. Rev. Clin. Lab. Sci. 42: 155–196PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media B.V. 2008

Authors and Affiliations

  • Shang-mian Yie
    • 1
  1. 1.Core Laboratory, Sichuan Provincial HospitalSichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalChengdu, SichuanPeoples Republic of China

Personalised recommendations