Advertisement

Breast Cancer Research and Treatment

, Volume 59, Issue 1, pp 69–76 | Cite as

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

  • Mårten Fernö
  • Olle Stål
  • Bo Baldetrop
  • Thomas Hatschek
  • Ann-Christine Källström
  • Per Malmström
  • Bo Nordenskjöld
  • Stefan Rydén
Article

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.

estrogen and progesterone receptor S-phase fraction tamoxifen breast cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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, 1992Google Scholar
  2. 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, 1996Google Scholar
  3. 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, 1996Google Scholar
  4. 4.
    Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351: 1451-1467, 1998Google Scholar
  5. 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 337-343Google Scholar
  6. 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, 1992Google Scholar
  7. 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, 1990Google Scholar
  8. 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, 1992Google Scholar
  9. 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, 1993Google Scholar
  10. 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, 1995Google Scholar
  11. 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, 1995Google Scholar
  12. 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, 1978Google Scholar
  13. 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, 1981Google Scholar
  14. 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, 1982Google Scholar
  15. 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, 1985Google Scholar
  16. 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, 1989Google Scholar
  17. 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, 1986Google Scholar
  18. 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, 1983Google Scholar
  19. 19.
    Thornthwaite JT, Sugarbaker EV, Temple WJ: Preparation of tissues for DNA flow cytometric analysis. Cytometry 1: 229-237, 1980Google Scholar
  20. 20.
    Lee GM, Thornthwaite JT, Rasch EM: Picogram per cell determination of DNA by flow cytofluorometry. Anal Biochem 137: 221-226, 1984Google Scholar
  21. 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, 1989Google Scholar
  22. 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, 1984Google Scholar
  23. 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, 1975Google Scholar
  24. 24.
    Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958Google Scholar
  25. 25.
    Cox DR: Regression models and life-tables. J R Stat Soc (B) 34: 187-220, 1972Google Scholar
  26. 26.
    Horwitz KB, McGuire WL, Pearson OH, Segaloff A: Predicting response to endocrine therapy in human breast cancer. A hypothesis. Science 189: 726-727, 1975Google Scholar
  27. 27.
    Early Breast Cancer Trialists' Collaborative Group: Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352: 930-942, 1998Google Scholar
  28. 28.
    Swain SM: Tamoxifen: the long and short of it. Editorial. J Natl Cancer Inst 88: 1510-1512, 1996Google Scholar
  29. 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), 1997Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Mårten Fernö
    • 1
  • Olle Stål
    • 2
  • Bo Baldetrop
    • 1
  • Thomas Hatschek
    • 2
  • Ann-Christine Källström
    • 3
  • Per Malmström
    • 1
  • Bo Nordenskjöld
    • 2
  • Stefan Rydén
    • 4
  1. 1.Department of OncologyUniversity HospitalLund
  2. 2.Department of OncologyUniversity HospitalLinköping
  3. 3.Department of Surgery, HospitalNorrköping
  4. 4.Department of Surgery, HospitalÄngelholmSweden

Personalised recommendations