Breast Cancer Research and Treatment

, Volume 48, Issue 1, pp 1–9

The prognostic contribution of estrogen and progesterone receptor status to a modified version of the Nottingham Prognostic Index

  • K. Collett
  • R. Skjærven
  • B.O. Mæhle


The aim of this study was to test the prognostic contribution of estrogen (ER) and progesterone (PgR) receptor status to an index consisting of the number of positive lymph nodes, the mean nuclear area of the breast cancer cells (MNA), and tumour diameter. This index is compared with a Danish index, which includes the same factors but uses histological grade instead of MNA. The Danish index has been developed from the Nottingham Prognostic Index (NPI). In the present study of 1629 breast cancer patients the Cox proportional hazard method is used to examine the time-dependency of the index, and to test for interaction between the index and the hormone receptors. The index sorts the patients into groups with low, intermediate, and high risk of dying. Logistic regression analysis is used to report the sensitivity and specificity of the index with and without ER and PgR. Our index gave information comparable to that of the Danish group. However, the information given by our index is time-dependent, its strength being weaker after 5-year of follow-up. PgR and ER add information to high risk patients, but only in the first 5-year period. High risk patients with positive hormone receptors have a prognosis similar to intermediate risk ones. PgR increases the ability of the index to predict breast cancer deaths correctly by 5 percent in high risk patients. In conclusion, PgR and ER act differently in groups of patients with different risk levels when time-dependency is considered. This indicates biological differences in subgroups as defined by the index.

breast cancer estrogen receptor status interaction effects progesterone receptor status prognostic index time-dependency 


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  1. 1.
    Miller WR, Ellis IO, Sainsbury JRC, Dixon JM: ABC of breast diseases. Prognostic factors. Br Med J 309: 1573–1576, 1994Google Scholar
  2. 2.
    Haybittle JL, Blamey RW, Elston CW, Johnson J, Doyle PJ, Campbell FC, Nicholson RI, Griffiths K: A prognostic index in primary breast cancer. Br J Cancer 45: 361–366, 1982Google Scholar
  3. 3.
    Balslev I, Axelsson CK, Zedeler K, Rasmussen BB, Carstensen B, Mouridsen HT: The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG). Breast Cancer Res Treat 32: 281–290, 1994Google Scholar
  4. 4.
    Uyterlinde AM, Baak JPA, Schipper NW, Peterse H, Matze E, Meijer CJL: Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breastcancer patients with long follow-up. Int J Cancer 45: 1–7, 1990Google Scholar
  5. 5.
    Baak JPA, Van Dop H, Kurver PHJ, Hermans J: The value of morphometry to classic prognosticators in breast cancer. Cancer 56: 374–382, 1985Google Scholar
  6. 6.
    Aaltomaa S, Lipponen P, Eskelinen M, Kosma V-M, Marin S, Alhava E, Syrjänen K: Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer. Int J Cancer 49: 886–892, 1991Google Scholar
  7. 7.
    Mæhle BO, Thoresen S, Skjærven R, Hartveit F: Mean nuclear area and histological grade of axillary-node tumour in breast cancer, related to prognosis. Br J Cancer 46: 95–100, 1982Google Scholar
  8. 8.
    Baak JPA, Kurver PHJ, De Snoo-Niewlaat AJE, De Graef S, Makkink B, Boon ME: Prognostic indicators in breast cancer – morphometric methods. Histopathol 6: 327–339, 1982Google Scholar
  9. 9.
    Collett K, Hartveit K, Skjærven R, Mæhle BO: Prognostic role of oestrogen and progesterone receptors in patients with breast cancer: relation to age and lymph node status. J Clin Pathol 49: 920–925, 1996Google Scholar
  10. 10.
    Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Béraud T, Gómez F: The predictive value of estrogen and progesterone receptors' concentrations on the clinical behavior of breast cancer in women. Clinical correlation on 547 patients. Cancer 57: 1171–1180, 1986Google Scholar
  11. 11.
    Kinne DW, Ashikari R, Butler A, Menendez-Botet C, Rosen PP, Schwartz M: Estrogen receptor protein in breast cancer as a predictor of recurrence. Cancer 47: 2364–2367, 1981Google Scholar
  12. 12.
    Blamey RW, Bishop HM, Blake JRS, Doyle PJ, Elston CW, Haybittle JL, Nicholson RI, Griffiths K: Relationship between primary breast tumor receptor status and patient survival. Cancer 46: 2765–2769, 1980Google Scholar
  13. 13.
    Mathiesen O, Bonderup O, Carl J, Panduro J, Pedersen KO: The prognostic value of estrogen and progesterone receptors in female breast cancer. Acta Oncol 30: 691–695, 1991Google Scholar
  14. 14.
    Saez S, Cheix F, Mayer M: Estrogen and progesterone receptors as prognostic factors in early breast cancer. Rec Results Cancer Res 91: 192–198, 1984Google Scholar
  15. 15.
    Mason BH, Holdaway IM, Mullins PR, Yee LH, Kay RG: Progesterone and estrogen receptors as prognostic variables in breast cancer. Cancer Res 43: 2985–2990, 1983Google Scholar
  16. 16.
    Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22: 207–219, 1992Google Scholar
  17. 17.
    Dixon WJ: BMDP Statistical Software. Berkeley, University of California Press, 1990Google Scholar
  18. 18.
    Rothman KJ, Greenland S, Walker AM: Concepts of interaction. Am J Epidemiol 112: 467–470, 1980Google Scholar
  19. 19.
    Lupu R, Lippman ME: The role of erbB2 signal transduction pathways in human breast cancer. Breast Cancer Res Treat 27: 83–93, 1993Google Scholar
  20. 20.
    Mittra IM, Redkar AA, Badwe RA: Prognosis of breast cancer: Evidence of interaction between c-erbB-2 overexpression and number of involved axillary lymph nodes. J Surg Oncol 60: 106–111, 1995Google Scholar
  21. 21.
    Clark GM: Prognostic and predictive factors. In: Harris JR, Lippman ME, Morrow M, Hellman S (eds) Diseases of the Breast. Lippincott-Raven Publishers, Philadelphia, 1996, p 476Google Scholar
  22. 22.
    Tandon AK, Clark GM, Chamness GC, Chirgwin JM, McGuire WL: Cathepsin D and prognosis in breast cancer. N Engl J Med 322: 297–302, 1990Google Scholar
  23. 23.
    Remvikos Y, Magdelenat H, Dutrillaux B: Genetic evolution of breast cancer III: Age-dependent variations in the correlations between biological indicators of prognosis. Breast Cancer Res Treat 34: 25–33, 1995Google Scholar
  24. 24.
    Fentiman IS, Cuzick J, Millis RR, Hayward JL: Which patients are cured of breast cancer? Br Med J 289: 1108–1111, 1984Google Scholar
  25. 25.
    Stenkvist B, Bengtsson E, Dahlqvist B, Eklund G, Eriksson O, Jarkrans T, Nordin B: Predicting breast cancer recurrence. Cancer 50: 2884–2893, 1982Google Scholar
  26. 26.
    Toikkanen SP, Kujari HP, Joensuu H: Factors predicting late mortality from breast cancer. Eur J Cancer 27: 586–591, 1991Google Scholar
  27. 27.
    Aaltomaa S, Lipponen P, Eskelinen M, Kosma V-M, Marin S, Alhava E, Syrjänen K: Prognostic factors after 5 years of follow-up. Oncology 49: 93–98, 1992Google Scholar
  28. 28.
    Gray RJ: Flexible methods for analyzing survival data using splines, with applications to breast cancer prognosis. J Am Stat Assoc 87: 942–951, 1992Google Scholar
  29. 29.
    Zahl PH, Tretli S: Long-term survival of breast cancer in Norway by age and clinical stage. Stat Med 16: 1–15, 1997Google Scholar
  30. 30.
    Todd JH, Dowle C, Williams MR, Elston CW, Ellis IO, Hinton CP, Blamey RW, Haybittle JL: Confirmation of a prognostic index in primary breast cancer. Br J Cancer 56: 489–492, 1987Google Scholar
  31. 31.
    Early Breast Cancer Trialists' Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339: 1–115, 71–85, 1992Google Scholar
  32. 32.
    Gundersen S, Hannisdal E, Søreide JA, Skarstein A, Varhaug JE: Adjuvant tamoxifen for pre-and postmenopausal women with estrogen receptor positive, node positive breast cancer: A randomized study. Breast Cancer Res Treat 36: 49–53, 1995Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • K. Collett
    • 1
  • R. Skjærven
    • 2
  • B.O. Mæhle
    • 1
  1. 1.Department of PathologyThe Gade InstituteNORWAY
  2. 2.Section for Medical Informatics and StatisticsUniversity of Bergen, Haukeland HospitalBergenNorway

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