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Node-Negative Breast Cancer: Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells

  • Nikos Xenidis
  • Maria Perrakis
  • S. Kakolyris
  • Dimitris Mavroudis
  • Vassilis Georgoulias
Part of the Methods of Cancer Diagnosis, Therapy and Prognosis book series (HAYAT, volume 1)

As a result of increased mammography screening programs, the majority of patients with breast cancer in recent years present with early-stage disease because the screening-detected tumors are significantly smaller than symptomatic or palpable tumors and frequently without axillary lymph node involvement. Metastatic involvement in the axillary lymph nodes is a powerful prognostic factor. Although the Early Breast Cancer Trialists’ Collaborative Group (2005) has shown a direct relationship between the number of involved nodes and the clinical outcome; nearly 30% of patients with node-negative breast cancer will present distant recurrence and will die as a result of their disseminated disease. This observation suggests that despite the general model of tumor cell dissemination, through the lymphatogenous route in the regional lymph nodes, there is also a direct haematogenous tumor cell dissemination that bypasses the lymphogenous. Thus, breast cancer detection at early stages does not ensure the definitive cure due to unpredictable invasiveness and metastatic potential of tumor cells.

Keywords

Breast Cancer Circulate Tumor Cell Minimal Residual Disease Disseminate Tumor Cell Early Breast Cancer Trialist 
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.

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References

  1. Aaltomaa, S., Lipponen, P., Eskelinen, M., Kosma, V.M., Marin, S., Alhava, E., and Syrjanen, K. 1992. Mitotic indexes as prognostic predictors in female breast cancer. J. Cancer Res. Clin. Oncol. 118: 75–81PubMedCrossRefGoogle Scholar
  2. Adair, F., Berg, J., Joubert, L., and Robbins, G.F. 1974. Long-term followup of breast cancer patients: the 30-year report. Cancer 33: 1145–1150PubMedCrossRefGoogle Scholar
  3. Anker, P., Mulcahy, H., Chen, X.Q., and Stroun, M. 1999. Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev. 18: 65–73PubMedCrossRefGoogle Scholar
  4. Baak, J.P., van Diest, P.J., Voorhorst, F.J., der Wall, E., Beex, L.V., Vermorken, J.B., Janssen, E.A., and Gudlaugsson, E. 2007. The prognostic value of proliferation in lymph node-negative breast cancer patients is age dependent. Eur. J. Cancer 43: 527–535PubMedCrossRefGoogle Scholar
  5. Balic, M., Lin, H., Young, L., Hawes, D., Giuliano, A., McNamara, G., Datar, R.H., and Cote, R.J. 2006. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin. Cancer Res. 12: 5615–5621PubMedCrossRefGoogle Scholar
  6. Braun, S. and Pantel, K. 1999. Biological characteristics of micrometastatic cancer cells in bone marrow. Cancer Metastasis Rev. 18: 75–90PubMedCrossRefGoogle Scholar
  7. Braun, S., Vogl, F.D., Naume, B., Janni, W., Osborne, M.P., Coombes, R.C., Schlimok,G., Diel, I.J., Gerber, B., Gebauer, G., Pierga, J.Y., Marth, C., Oruzio, D., Wiedswang, G., Solomayer, E.F., Kundt, G., Strobl, B., Fehm, T., Wong, G.Y., Bliss, J., Vincent-Salomon, A., and Pantel, K. 2005. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 353: 793–802PubMedCrossRefGoogle Scholar
  8. Brown, R.W., Allred, C.D., Clark, G.M., Osborne, C.K., and Hilsenbeck, S.G. 1996. Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer. Clin. Cancer Res. 2: 585–592PubMedGoogle Scholar
  9. Bryant, J., Fisher, B., Gunduz, N., Costantino, J.P., and Emir, B. 1998. S-phase fraction combined with other patient and tumor characteristics for the prognosis of node-negative, estrogen-receptor-positive breast cancer. Breast Cancer Res. Treat. 51: 239–253PubMedCrossRefGoogle Scholar
  10. Carter, C.L., Allen, C., and Henson, D.E. 1989. Relation of tumor size, lymph node status and survival in 24,740 breast cancer cases. Cancer 63: 181–187PubMedCrossRefGoogle Scholar
  11. De Placido, S., De Laurentiis, M., Carlomagno, C., Gallo, C., Perrone, F., Pepe, S., Ruggiero, A., Marinelli, A., Pagliarulo, C., Panico, L., Pettinato, G., Petrella, G., and Bianco, A.R. 2003. Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer. Clin. Cancer Res. 9: 1039–1046PubMedGoogle Scholar
  12. Donegan, W.L. (1997) Tumor-related prognostic factors for breast cancer. C.A. Cancer J. Clin. 47: 28–51CrossRefGoogle Scholar
  13. Early Breast Cancer Trialists' Collaborative Group. 1998. Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 351: 1451–1467CrossRefGoogle Scholar
  14. Early Breast Cancer Trialists' Collaborative Group. 2005. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365: 1687–1717CrossRefGoogle Scholar
  15. Fehm, T., Becker, S., Becker-Pergola, G., Sotlar, K., Gebauer, G., Durr-Storzer, S., Neubauer, H., Wallwiener, D., and Solomayer, E.F. 2006. Presence of apoptotic and non apoptotic disseminated tumor cells reflect response to neoadjuvant systemic therapy (NST) in breast cancer. Breast Cancer. Res. 8: R60Google Scholar
  16. Hu, X.C., Loo, W.T., and Chow, L.W. 2003. Surgery related shedding of breast cancer cells as determined by RT-PCR assay. J. Surg. Oncol. 82: 228–232PubMedCrossRefGoogle Scholar
  17. 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
  18. Le Doussal, V., Tubiana-Hulin, M., Friedman, S., Hacene, K., Spyratos, F., and Brunet, M. 1989. Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a mul-tivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 64: 1914–1921PubMedCrossRefGoogle Scholar
  19. Lee, A.H., Pinder, S.E., Macmillan, R.D., Mitchell, M., Ellis, I.O., Elston, C.W., and Blamey, R.W. 2006. Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma. Eur. J. Cancer 42: 357–362PubMedCrossRefGoogle Scholar
  20. McGuire, W.L. 1991. Breast cancer prognostic factors: evaluation guidelines. J. Natl. Cancer Inst. 83: 154–155PubMedCrossRefGoogle Scholar
  21. McGuire, W.L., Tandon, A.K., Allred, D.C., Chamness, G.C., and Clark, G.M. 1990. How to use prognostic factors in axillary node-negative breast cancer patients. J. Natl. Cancer Inst. 82: 1006–1015PubMedCrossRefGoogle Scholar
  22. Press, M.F., Bernstein, L., Thomas, P.A., Meisner, L.F., Zhou, J.Y., Ma, Y., Hung, G., Robinson, R.A., Harris, C., El-Naggar, A., Slamon, D.J., Phillips, R.N., Ross, J.S., Wolman, S.R., and Flom, K.J. 1997. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J. Clin. Oncol. 15: 2894–2904PubMedGoogle Scholar
  23. Ravdin, P.M. 2001. Is Her2 of value in identifying patients who particularly benefit from anthracy-clines during adjuvant therapy? A qualified yes. J. Natl. Cancer Inst. Monogr. 30: 80–84PubMedGoogle Scholar
  24. Roetger, A., Merschjann, A., Dittmar, T., Jackisch, C., Barnekow, A., and Brandt, B. 1998. Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am. J. Pathol. 153: 1797–1806Google Scholar
  25. Ruud, P., Fodstad, O., and Hovig, E. 1999. Identification of a novel cytokeratin 19 pseudog-ene that may interfere with reverse transcriptase-polymerase chain reaction assays used to detect micrometastatic tumor cells. Int. J. Cancer 80: 119–125PubMedCrossRefGoogle Scholar
  26. Seidman, A.D., Fornier, M., Esteva, F.J., Tan, L., Kaptain, S., Bach, A., Panageas, K.S., Arroyo, C., Valero, V. , Currie, V., Gilewski, T., Theodoulou, M., Moynahan, M.E., Moasser, M., Sklarin, N., Dickler, M., D'Andrea, G., Cristofanilli, M., Rivera, E., Hortobagyi, G.N., Norton, L., and Hudis, C. 2001. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophe-notype and gene amplification. J. Clin. Oncol. 19: 2587–2595PubMedGoogle Scholar
  27. Sidransky, D. 1997. Nucleic acid-based methods for the detection of cancer. Science 278: 1054–1059PubMedCrossRefGoogle Scholar
  28. 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: evaluation of their prognostic significance. J. Clin. Oncol. 20: 3404–3412CrossRefGoogle Scholar
  29. Thiery, J.P. 2002. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2: 442–454PubMedCrossRefGoogle Scholar
  30. Thurm, H., Ebel, S., Kentenich, C., Hemsen, A., Riethdorf, S., Coith, C., Wallwiener, D., Braun, S., Oberhoff, C., Janicke, F., and Pantel, K. 2003. Rare expression of epithelial cell adhesion molecule on residual micrometastatic breast cancer cells after adjuvant chemotherapy. 9: 2598–2604PubMedGoogle Scholar
  31. Wiedswang, G., Borgen, E., Schirmer, C., Karesen, R., Kvalheim, G., Nesland, J.M., and Naume, B. 2006. Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer. Int. J. Cancer. 118: 2013–2019PubMedCrossRefGoogle Scholar
  32. Xenidis, N., Vlachonikolis, I., Mavroudis, D., Perraki, M., Stathopoulou, A., Malamos, N., Kouroussis, C., Kakolyris, S., Apostolaki, S., Vardakis, N., Lianidou, E., and Georgoulias, V. 2003. Peripheral blood circulating cytok-eratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann. Oncol. 14: 849–55PubMedCrossRefGoogle Scholar
  33. Xenidis, N., Perraki, M., Kafousi, M., Apostolaki, S., Bolonaki, I., Stathopoulou, A., Kalbakis, K., Androulakis, N., Kouroussis, C., Pallis, T., Christophylakis, C., Argyraki, K., Lianidou, E.S., Stathopoulos, S., Georgoulias, V. , and Mavroudis, D. 2006. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J. Clin. Oncol. 24: 3756–3762PubMedCrossRefGoogle Scholar
  34. Yamauchi, H., Stearns, V., and Hayes, D.F. 2001. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J. Clin. Oncol. 19: 2334–2356PubMedGoogle Scholar
  35. Zieglschmid, V., Hollmann, C., and Bocher, O. 2005. Detection of disseminated tumor cells in peripheral blood. Crit. Rev. Clin. Lab. Sci. 42: 155–196Google Scholar

Copyright information

© Springer Science + Business Media B.V. 2008

Authors and Affiliations

  • Nikos Xenidis
    • 1
  • Maria Perrakis
    • 1
  • S. Kakolyris
    • 1
  • Dimitris Mavroudis
    • 1
  • Vassilis Georgoulias
    • 1
  1. 1.Department of Medical OncologyUniversity General Hospital of HeraklionHeraklionGreece

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