Skip to main content
Log in

Long term prognostic value of growth fraction determination by Ki-67 immunostaining in primary operable breast cancer

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

An immunohistochemical determination of the growth fraction (GF) with the Ki-67 monoclonal antibody has been performed in a prospective series of 140 patients with primary operable breast carcinoma. GF ranged from 0% to 43% Ki-67 stained cells with a median value of 8%. High GF (> 8%) was significantly associated with axillary node involvement (p = 0.006), aneuploidy (p = 0.008), histologic grade (p = 0.03), and S-phase fraction > 5% determined by flow cytometry (p = 0.01). After a median follow-up of 6 years, the univariate analysis did not show significant correlation between high GF and worse relapse-free survival (p = 0.10) or shorter overall survival. However, a multivariate analysis on relapse-free survival, performed in 127 comparable patients, showed that GF was an independent predictive factor (p = 0.03) together with nodal status (p = 0.00001), age under 45 years (p = 0.0008), and chemotherapy (0.006). In node negative patients, GF was still an independent prognostic indicator (p = 0.002) together with age under 45 years (p = 0.0003). Tumor proliferative activity evaluated by the monoclonal antibody Ki-67 appears to be an effective indicator of prognosis in breast cancer and could be of assistance in the decision making of adjuvant therapy in node negative patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Meyer JS, Friedman E, McRate MM, Bauer WC: Prediction of early course of breast carcinoma by thymidine labelling. Cancer 51: 1879–1886, 1983

    PubMed  Google Scholar 

  2. Tubiana M, Pejovic MJ, Chavaudra N, Contesso G, Malaise E: The long-term prognostic significance of the thymidine labelling index in breast cancer. Int J Cancer 33: 441–445, 1984

    PubMed  Google Scholar 

  3. Clark GM, Dressler LG, Marilyn AO, Pounds G, Oldaker T, McGuire W: Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med 320: 627–633, 1989

    PubMed  Google Scholar 

  4. Meyer JS, Coplin MD: Thymidine labeling index, flow cytometric S-phase measurement and DNA index in human tumors: comparisons and correlations. Am J Clin Pathol 89: 586–595, 1988

    PubMed  Google Scholar 

  5. Viehl P, Chevillard S, Mosseri V, Donatini B, Magdelenat H: Ki-67 index and S-phase fraction in human breast carcinomas. Am J Clin Pathol 94: 681–686, 1990

    PubMed  Google Scholar 

  6. Remvikos Y: Prognostic value of the S-phase fraction of breast cancer. Br J Cancer 68: 433–434, 1993

    PubMed  Google Scholar 

  7. Gerdes J, Li L, Schlüter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD: Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138: 867–873, 1991

    PubMed  Google Scholar 

  8. Schlüter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD, Gerdes J: The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol 123: 513–522, 1993

    PubMed  Google Scholar 

  9. Gaglia P, Bernardi A, Venesio T, Caldarola B, Lauro D, Cappa APM, Calderini P, Liscia DS: Cell proliferation of breast cancer evaluated by anti-BrdU anti-Ki67 antibodies: its prognostic value on short-term recurrences. Eur J Cancer 29A: 1509–1513, 1993

    PubMed  Google Scholar 

  10. Veronese SM, Gambacorta M, Gottardi O, Scanzi F, Ferrari M, Lampertico P: Proliferation index as a prognostic marker in breast cancer. Cancer 81: 3926–3931, 1993

    Google Scholar 

  11. Gerdes J, Schwab U, Lemke H, Stein H: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31: 13–20, 1983

    PubMed  Google Scholar 

  12. Osborne CK: Prognostic factors for breast cancer: have they met their promise? J Clin Oncol 10: 679–682, 1992

    PubMed  Google Scholar 

  13. Sigurdsson H, Baldetorp B, Borg A, Dalberg M, Fernö M, Killander D, Olsson H: Indicators of prognosis in node-negative breast cancer. N Engl J Med 322: 1045–1053, 1990

    PubMed  Google Scholar 

  14. Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–366, 1957

    PubMed  Google Scholar 

  15. Magdelénat H, Lainé-Bidron C, Merle S, Zajdela A: Estrogen and progestin receptor assay in fine needle aspirates of breast cancer: methodological aspect. Eur J Cancer Clin Oncol 23: 425–431, 1987

    PubMed  Google Scholar 

  16. Baisch H, Gohde W, Linden WA: Mathematical analysis of pulse-cytophotometric data to determine the fraction of cells in the various phases of cell cycle. Radiat Environ Biophys 12: 31–39, 1975

    PubMed  Google Scholar 

  17. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958

    Google Scholar 

  18. Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163–170, 1966

    PubMed  Google Scholar 

  19. Cox DR: Regression models and life tables (with discussion). J Stat Soc B 34: 187–220, 1972

    Google Scholar 

  20. Bouzubar N, Walker KJ, Griffiths K, Ellis IO, Elston CW, Robertson JFR, Blamey RW, Nicholson KI: Ki-67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer 59: 943–947, 1989

    PubMed  Google Scholar 

  21. Gasparini G, Pozza F, Meli S, Reitano M, Santini G, Bevilacqua P: Breast cancer cell kinetics: Immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-phase and with some features of tumor aggressiveness. Anti-Cancer Res 11: 2015–2022, 1991

    Google Scholar 

  22. Weickel W, Beck T, Mitze M, Knapstein PG: Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67. Breast Cancer Res Treat 18: 149–154, 1991

    PubMed  Google Scholar 

  23. Wintzer HO, Zipfel I, Schulte-Möntig J, Hellerich U, von Kleist S: Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 67: 421–428, 1991

    PubMed  Google Scholar 

  24. Gasparini G, Pozza F, Bevilacqua P, Meli S, Boracchi P, Reitano M, Santini G, Marubini E, Sainsbury JRC: Growth fraction (Ki-67 antibody) determination in early-stage breast carcinoma: histologic, clinical and prognostic correlations. The Breast 1: 92–99, 1992

    Google Scholar 

  25. Railo M, Nordling S, von Boguslawsky K, Leivonen M, Kyllönen L, von Smitten K: Prognostic value of Ki-67 immunolabelling in primary operable breast cancer. Br J Cancer 68: 579–583, 1993

    PubMed  Google Scholar 

  26. Rudas M, Gnant MFX, Mittlböck M, Neumayer R, Kummer A, Jakesz R, Reiner G, Reiner A: Thymidine labeling index and Ki-67 growth fraction in breast cancer: comparison and correlation with prognosis. Breast Cancer Res Treat 32: 165–176, 1994

    PubMed  Google Scholar 

  27. de la Rochefordière A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR, Durand JC, Pouillart P, Magdelénat H, Fourquet A: Age as prognostic factor in premenopausal breast carcinoma. Lancet 341: 1039–1043, 1993

    PubMed  Google Scholar 

  28. Sahin AA, Ro J, Ro JY, Blick MB, El-Naggar AK, Ordonnez NG, Fritsche HA, Smith TL, Hortobagyi GN, Ayala AG: Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Cancer 68: 549–557, 1991

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pierga, J.Y., Leroyer, A., Viehl, P. et al. Long term prognostic value of growth fraction determination by Ki-67 immunostaining in primary operable breast cancer. Breast Cancer Res Tr 37, 57–64 (1996). https://doi.org/10.1007/BF01806632

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01806632

Key words

Navigation