Skip to main content

Advertisement

SpringerLink
Log in

Der prognostische Stellenwert der Flowzytometrie beim Mammakarzinom

10-Jahres-Ergebnisse einer randomisierten Studie

The prognostic significance of DNA flowcytometry in human breast cancer

10-Year results of a randomised trial

  • Themenschwerpunkt: Therapiekonzepte Beim Operablen Mammakarzinom
  • Published:
Acta Chirurgica Austriaca Aims and scope Submit manuscript

Zusammenfassung

Tumoren von 191 Mammakarzinompatientinnen einer randomisierten Studie werden mit Hilfe der DNA-Flowzytometrie evaluiert. DNA-Index (DNI) und der Anteil der Zellen in der Synthesephase (SPF) werden auf ihre Korrelationen mit prognostischen Faktoren hin untersucht. Die prognostische Bedeutung dieser Parameter wird mit einer mittleren Nachbeobachtungszeit von mehr als 10 Jahrens sowohl univariat als auch multivariat untersucht. Korrleation bestehen zwischen DNI und SPF (p=0,0001) sowie zwischen DNI und SPF einerseits und wichtigen bekannten prognostischen Faktoren wie Nodalstatus, Tumorgröße und Grading andererseits. In der Kaplan-Meyer-Analyse zeigt sich, daß DNI nicht zwischen Patientinnengruppen mit geringem und mit hohem Sterbe-bzw. Rezidivrisiko unterscheiden kann. Im Gegensatz dazu kann für SPF die zweitstärkste univariate Bedeutung nachgewiesen werden (p=0,0021). Auch im Cox-Modell ist SPF nach dem Nodalstatus der bedeutendste unabhängige prognostische Faktor (relatives Sterberisiko für Patientinnen über 11% SPF: +110%). Durch die Kombination von Nodalstatus und SPF können die Patientinnen in exakte prognostische Untergruppen eingeteilt werden (p<0,00001), wodurch in Zukunft wesentliche Erkenntnisse über die geeignetste adjuvante Therapieform gewonnen werden können. Routinemäßige Tumor-DNA-Flowzytometrie muß daher zum Standard moderner Tumordiagnostik gehören.

Summary

Breast carcinomas from 191 patients of a controlled clinical trial were evaluated by means of DNA flowcytometry. Correlations between DNA index (DNI) and fraction of cells in S-phase (SPF) and other prognostic parameters are determined. The predictive power of these factors is evaluated after a follow-up of more than 10 years. There are strong correlations between DNI and SPF (p=0,0001) and between flowcytometry parameters and other factors such as axillary lymph node involvement, tumor size and histologic grading. In a Kaplan-Meyer analysis DNI failes to provide prognostic information, whereas SPF turns out to differentiate between patients at high and low risk for relapse and death (p=0,0021). In the multivariate Cox-model, too, SPF is an important prognostic parameter (relative risk: +110%), surpassed only by nodal involvement. By combination of these 2 variables, patients can be divided into 4 prognostic subgroups (p<0,00001). Data from DNA flowcytometry can be of great importance for the decision which adjuvant therapy is choosen for an individual patient and should be standard in modern tumor diagnostics.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Fisher B, Bauer M, Wickerham DL, et al: Relation of number of positive axiallary nodes to the prognosis of patients with primary breast cancer. Cancer 1983;542:1551–1557.

    Article  Google Scholar 

  2. Fisher B, Slack NH, Bross IDJ, et al: Cancer and the breast: Size of the neoplasm and prognosis. Cancer 1969;24:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  3. Valagussa P, Bonadonna G, Veronesi U: Patterns of relapse and survival following radical mastectomy. Cancer 1978;41:1170–1178.

    Article  PubMed  CAS  Google Scholar 

  4. Fisher B, Redmond C, Fisher ER, et al: Relative worth of estorgen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: Findings from National Surgical Andjuvant Breast and Bowel Project protocol B-06. J Clin Oncol 1988;6:1076–1087.

    PubMed  CAS  Google Scholar 

  5. Knight WA, Livingston RB, Gregory EJ, et al: Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 1977;37:4669–4671.

    PubMed  CAS  Google Scholar 

  6. Clark GM, McGuire WL, Hubay CA, et al: Progesterone receptors as a prognostic factor in stage II breast cancer. N Engl J Med 1983;309:1343–1347.

    PubMed  CAS  Google Scholar 

  7. Tubiana M, Pejovic MJ, Renaud A, Contesso G, Chavaudra G, Gioanni N, Malaise EP: Kinetic parameters and the course of disease in breast cancer. Cancer 1981;47:937–943.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Slamon DJ, Godolphin W, Jones LA, et al.: Studies of the HER-2/neu protooncogen in human breast and ovarian cancer. Science 1989;244:707–712.

    Article  PubMed  CAS  Google Scholar 

  10. Sainsbury JR, Farndon JR, Needham GK, et al: Epidermal-growth-factor receptor status as predictor for early recurrence of and death from breast cancer. Lancet 1987;1:1398–1402.

    PubMed  CAS  Google Scholar 

  11. Tandon AK, Clark GM, Chammess GC, et al: Cathepsin D and prognosis in breast cancer. N Engl J Med 1990;322:297–302.

    Article  PubMed  CAS  Google Scholar 

  12. Thor A, Benz C, Moore D, Goldman E, Edgerton S, Landry J, et al: Stress response protein (srp-27) determination in primary human breast carcinomas: Clinical, histologic, and prognostic correlations. J Natl Cancer Inst 1990;83:170–178.

    Article  Google Scholar 

  13. Colm H, Henry JA, May FEB, Westley BR, Angus B, Lennard TWJ: Expression of the antimetastatic gene nm23 in human breast cancer: An association with good prognosis. J Natl Cancer Inst 1991;83:281–285.

    Article  Google Scholar 

  14. Hedley DW, Rugg CA: Association of DNA index and S-phase fraction with prognosis of N+ early breast cancer. Cancer Res 1987;47:4729–4735.

    PubMed  CAS  Google Scholar 

  15. Kalloniemi OP, Blanco G, Alovaikko M, et al: Tumor DNA ploidy as an independent prognostic factor in breast cancer. Br J Cancer 1987;56:637–642.

    Google Scholar 

  16. Jakesz R, Reiner G, Schemper M, et al: Significant survival benefit of node-negative breast cancer patients treated with adjuvant chemotherapy: Seven-year results. Rec Results Cancer Res 1988;115:180–184.

    Google Scholar 

  17. Pocock SJ, Simon R: Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975;31:103–115.

    Article  PubMed  CAS  Google Scholar 

  18. Bloom HJG, Richardson WW: Histologic grading and prognosis in breast cancer. Br J Cancer 1957;11:359–377.

    PubMed  CAS  Google Scholar 

  19. Jakesz R, Dittrich C, Hanusch J, et al: Simultaneous and sequential determination of steroid hormone receptors in human breast cancer. Ann Surg 1985;3:305–310.

    Article  Google Scholar 

  20. Schutte B, Reynders MMJ, Bosman FTG, et al: Flow cytometric determination of DNA ploidy level in isolated nuclei from paraffin embedded tissue. Cytometry 1986;6:26–30.

    Article  Google Scholar 

  21. Hedley DW: Flow cytometry using paraffin-embedded tissue: Five years on. Cytometry 1989;10:229–241.

    Article  PubMed  CAS  Google Scholar 

  22. Vindelov LL, Christensen U, Nissen NI: A detergent trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 1983;3:323–327.

    Article  PubMed  CAS  Google Scholar 

  23. Kutte TE, Muss HB, Cooper MR, et al: The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients. Cancer 1990;66:1810–1816.

    Article  Google Scholar 

  24. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Ass 1987;53:457–481.

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Cox DR: Regression models and life-tables. J R Stat Soc (B) 1972;34:187–220.

    Google Scholar 

  27. Sigurdsson H, Baldetorp B, Borg A, et al: Indicators of prognosis in node negative breast cancer. N Engl J Med 1990;322:1045–1053.

    Article  PubMed  CAS  Google Scholar 

  28. Kallonierni OP, Blanco G, Alvaikko M, et al: Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase. Cancer 1988;62:2183–2190.

    Article  Google Scholar 

  29. Clark GM, Dressler LG, Owens MA, Pounds G, Oldaker T, McGuire WL: Prediction of relapse or survival in patients with node negative breast cancer by DNA flow cytometry. N Engl J Med 1989;320:627–633.

    Article  PubMed  CAS  Google Scholar 

  30. Keyhani-Rofagha S, O'Toole RV, Farrar WB, et al.: Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma. Cancer 1990;65:1577–1582.

    Article  PubMed  CAS  Google Scholar 

  31. Owanati AA, Robins RA, Hinton C, et al: Tumour aneuploidy, prognostic parameters and survival in primary breast cancer. Br J Cancer 1987;55:449–454.

    Google Scholar 

  32. Ewers SB, Baldetorp B, Killander D, Langstrom E: Flow cytometry DNA ploidy and number of cell populations in the primary breast cancer and their correlation to the prognosis. Acta Oncol 1989;28:913–918.

    PubMed  CAS  Google Scholar 

  33. Cornelisse CJ, van de Velde CJ, Caspers RJ, Moolenaar AJ, Hermans J: DNA ploidy and survival in breast cancer patients. Cytometry 1987;8:225–234.

    Article  PubMed  CAS  Google Scholar 

  34. Kallonierni OP, Hietanen T, Mattila J, Lehtinen M, Lauslahti K, Koivula T, et al: Aneuploid DNA content and high S-phase fraction of tumour cells are related to poor prognosis in patients with primary breast cancer. Eur J Cancer Clin Oncol 1987;23:277–282.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chirurgischen Universitätsklinik Wien, Alserstraße 4, A-1097, Wien

    M. Grant, M. Schemper, G. Reiner & R. Jakesz

  2. Department für Innere Medizin, Universität Limburg, Maastricht, Niederlande

    G. Blijham, M. Reynders, B. Schutte & C. van Asche

  3. Pathologisch-Anatomischen Institut der Universität Wien, Wien, Österreich

    A. Reiner

  4. Universitätsklinik für Frauenheilkunde und Geburtshilfe Wien, Wien, Österreich

    J. Spona

  5. Klinischen Abteilung für Onkologie der Universität Wien, Wien, Österreich

    G. Steger

Authors
  1. M. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Blijham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Schemper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Reiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Reiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Spona
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Reynders
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. Schutte
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. van Asche
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G. Steger
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R. Jakesz
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Herrn Prof. Dr.A. Fritsch zum 65. Geburtstag gewidmet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grant, M., Blijham, G., Schemper, M. et al. Der prognostische Stellenwert der Flowzytometrie beim Mammakarzinom. Acta Chir Austriaca 23, 43–48 (1991). https://doi.org/10.1007/BF02658924

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02658924

Schlüsselwörter

Search

Navigation