Skip to main content
SpringerLink
Log in

Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels

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

Abstract

A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment.

In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.

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

Similar content being viewed by others

References

  1. Early Breast Cancer Trialists' Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339: 1-15, 71-85, 1992

    Google Scholar 

  2. Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschênes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AHG, Feldman MI, Farrar W, Evans J, Lickley HL: Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen-receptor-positive tumors. J Natl Cancer Inst 88: 1529-1542, 1996

    Google Scholar 

  3. Swedish Breast Cancer Cooperative Group: Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. J Natl Cancer Inst 88: 1543-1549, 1996

    Google Scholar 

  4. Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351: 1451-1467, 1998

    Google Scholar 

  5. McGuire WL: An update on estrogen and progesterone receptors in prognosis for primary and advanced breast cancer. In: Iacobelli S et al. (eds) Hormones and Cancer. Raven Press, New York, 1980, pp 337-343

    Google Scholar 

  6. Clark GM, Mathieu M-C, Owens MA, Dressler LG; Eudey L, Tormey DC, Osborne CK, Gilchrist KW, Mansour EG, Abeloff MD, McGuire WL: Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients. J Clin Oncol 10: 428-432, 1992

    Google Scholar 

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

    Google Scholar 

  8. Stål O, Carstensen J, Hatschek T, Nordenskjöld B: Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients. Br J Cancer 66: 706-711, 1992

    Google Scholar 

  9. Hedley DW, Clark GM, Cornelisse CJ, Killander D, Kute T, Merkel D: Consensus review of the clinical utility of DNA cytometry in carcinoma of the breast. Cytometry 14: 482-485, 1993

    Google Scholar 

  10. Fernö M, Baldetorp B, Bendahl P-O, Borg Å, Ewers S-B, Olsson H, Rydén S, Sigurdsson H, Killander D: Recurrencefree survival in breast cancer improved by adjuvant tamoxifen, especially for progesterone receptor positive tumors with a high proliferation. Breast Cancer Res Treat 36: 23-34, 1995

    Google Scholar 

  11. Baldetorp B, Bendahl P-O, Fernö M, Alanen K, Delle U, Falkmer U, Hansson-Aggesjö B, Höckenström T, Lindgren A, Mossberg L, Nordling S, Sigurdsson H, Stål O, Visakorpi T: Reproducibility in DNA flow cytometric analysis of breast cancer: Comparison of 12 laboratories' results for 67 sample homogenates. Cytometry 22: 115-127, 1995

    Google Scholar 

  12. Wrange Ö, Nordenskjöld B, Gustafsson J-Å: Cytosol estradiol receptor in human mammary carcinoma: An assay based on isoelectric focusing in polyacrylamide gel. Anal Biochem 85: 461-475, 1978

    Google Scholar 

  13. Wrange Ö, Humla S, Ramberg I, Gustafsson SA, Skoog L, Nordenskjöld B, Gustafsson J-Å: Progestin-receptor analysis in human breast cancer cytosol by isoelectric focusing in slabs of polyacrylamide gel. J Steroid Biochem 14: 141-148, 1981

    Google Scholar 

  14. Norgren A, Borg Å, Fernö M, Johansson U, Lindahl B, Tsiobanelis K: Improved method for assay of estradiol and progesterone receptors with special reference to breast cancer. Anticancer Res 2: 315-320, 1982

    Google Scholar 

  15. Fernö M, Borg A, Sellberg G: Enzyme immuno assay of the estrogen receptor in breast cancer biopsy samples. A comparison with isoelectric focusing. Acta Radiol Oncol 25: 171-175, 1985

    Google Scholar 

  16. Fernö M, Borg Å, Johansson U: Enzyme immunoassay of progesterone receptor in breast cancer biopsy samples. A comparison with the dextran coated charcoal method. Acta Oncol 28: 19-22, 1989

    Google Scholar 

  17. Norgren A, Fernö M, Borg Å: Observations on wet weight, protein and DNA as reference for steroid receptors in malignant mammary tumors. Anticancer Res 6: 59-64, 1986

    Google Scholar 

  18. Vindelöv LL, Christensen IJ, Nissen NI: A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3: 323-327, 1983

    Google Scholar 

  19. Thornthwaite JT, Sugarbaker EV, Temple WJ: Preparation of tissues for DNA flow cytometric analysis. Cytometry 1: 229-237, 1980

    Google Scholar 

  20. Lee GM, Thornthwaite JT, Rasch EM: Picogram per cell determination of DNA by flow cytofluorometry. Anal Biochem 137: 221-226, 1984

    Google Scholar 

  21. Baldetorp B, Dalberg M, Holst U, Lindgren G: Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm. Cytometry 10: 695-705, 1989

    Google Scholar 

  22. Hiddemann W, Schumann J, Andreeff M, Barlogie B, Herman CJ, Leif RC, Mayall BH, Murphy RF, Sandberg AA: Convention on nomenclature for DNA cytometry. Cytometry 14: 445-446, 1984

    Google Scholar 

  23. Baisch H, Gohde W, Linden WA: Analysis of PCP-data to determine the fraction of cells in various phases of the cell cycle. Radiat Environ Biophys 12: 31-39, 1975

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  26. Horwitz KB, McGuire WL, Pearson OH, Segaloff A: Predicting response to endocrine therapy in human breast cancer. A hypothesis. Science 189: 726-727, 1975

    Google Scholar 

  27. Early Breast Cancer Trialists' Collaborative Group: Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352: 930-942, 1998

    Google Scholar 

  28. Swain SM: Tamoxifen: the long and short of it. Editorial. J Natl Cancer Inst 88: 1510-1512, 1996

    Google Scholar 

  29. Delozier T, Spielmann M, Macé-Lesec'h J, Janvier M, Luboinski M, Asselain B, Julien JP, Weber B, Mauriac L, Petit JC, Kerbrat P, Malhaire JP, Vennin P, Leduc B, Van Tongelen K: Short-term versus lifelong adjuvant tamoxifen in early breast cancer (EBC): a randomized trial (TAM-01). J Clin Oncol 16: 128a (Abstract 451), 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, University Hospital, Lund

    Mårten Fernö, Bo Baldetrop & Per Malmström

  2. Department of Oncology, University Hospital, Linköping

    Olle Stål, Thomas Hatschek & Bo Nordenskjöld

  3. Department of Surgery, Hospital, Norrköping

    Ann-Christine Källström

  4. Department of Surgery, Hospital, Ängelholm, Sweden

    Stefan Rydén

Authors
  1. Mårten Fernö
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olle Stål
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Baldetrop
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Hatschek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ann-Christine Källström
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Per Malmström
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bo Nordenskjöld
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stefan Rydén
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fernö, M., Stål, O., Baldetrop, B. et al. Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels. Breast Cancer Res Treat 59, 69–76 (2000). https://doi.org/10.1023/A:1006332423620

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006332423620

Search

Navigation