Skip to main content
SpringerLink
Log in

Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis

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

Abstract

The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the ‘aggressive’ phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.

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. Kelsey JL, Fischer DB, Holford TR, Lovolsi VA, Mostow ED, Goldenberg IS: Exogenous estrogens and other factors in the epidemiology of breast cancer. J Natl Cancer Inst 67: 327–333, 1981

    Google Scholar 

  2. Key TJA, Pike MC: The role of estrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24: 29–43, 1988

    Google Scholar 

  3. Ewertz M: Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark. Int J Cancer 42: 177–181, 1988

    Google Scholar 

  4. Ries LG, Pollack ES, Young JL: Cancer patient survival: surveillance, epidemiology, and end results program, 1973–1979. J Natl Cancer Inst 70: 693–707, 1983

    Google Scholar 

  5. Rutqvist LE, Wallgren A, Nilsson B: Breast cancer a curable disease? A study of 14731 women with breast cancer from the Cancer Registry of Norway. Cancer 53: 1793–1800, 1984

    Google Scholar 

  6. De la Rochefordiere A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR, Durand J-C, Pouillart P, Magdelenat H, Fourquet A: Age as a prognostic factor in premenopausal breast carcinoma. Lancet 341: 1039–1043, 1993

    Google Scholar 

  7. Dutrillaux B, Gerbault-Seureau M, Remvikos Y, Zafrani B, Prieur M: Breast cancer genetic evolution I: Data from cytogenetics and DNA content. Breast Cancer Res Treat 19: 245–255, 1991

    Google Scholar 

  8. Magdelénat H, Gerbault-Seureau M, Lainé-Bidron C, Prieur M, Dutrillaux B: Genetic evolution of breast cancer II: Relationship with estrogen and progesterone receptor expression. Breast Cancer Res Treat, 22: 119–127, 1992

    Google Scholar 

  9. Remvikos Y, Gerbault-Seureau M, Magdelénat H, Dutrillaux B: Proliferative activity of breast cancers increase in the course of genetic evolution as defined by cytogenetic analysis. Breast Cancer Res Treat 23: 43–49, 1992

    Google Scholar 

  10. Meyer JS: Cell kinetics in selection and stratification of patients for adjuvant therapy of breast carcinoma. NCI Monogr 1: 25–28, 1986

    Google Scholar 

  11. Thorpe SM, Rose C, Rasmussen BB, Mouridsen HT, Bayer T, Keiding N: Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer. Cancer Res 47: 6126–6133, 1987

    Google Scholar 

  12. Kallioniemi OP, Hietanen T, Mattila J, Lehtinen M, Lauslahti K, Koivula T: 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 23: 277–282, 1987

    Google Scholar 

  13. Fisher B, Redmond C, Fisher ER, Caplan R, and other NSABP Investigators: Relative worth of estrogen and progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from the NSABP protocol B-06. J Clin Oncol 6: 1076–1087, 1988

    Google Scholar 

  14. Silvestrini R, Daidone MG, Valagussa P, Difronzo G, Mezzanotte G, Bonadonna G: Cell kinetics as a prognostic indicator in node-negative breast cancer. Eur J Cancer Clin Oncol 25: 1165–1171, 1989

    Google Scholar 

  15. Tubiana M, Pejovic MH, Koscielny S, Chavaudra N, Malaise E: Growth rate, kinetics of tumor cell proliferation, and long-term outcome in human breast cancer. Int J Cancer 44: 17–22, 1989

    Google Scholar 

  16. Stal O, Carstensen J, Rutqvist LE, Skoog L, Klintenberg C, Nordenskjold B: Prognostic value of DNA ploidy and S-phase fraction in relation to estrogen receptor content and clinicopathological variables in primary breast cancer. Eur J Cancer Clin Oncol 25: 301–309, 1989

    Google Scholar 

  17. 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. New EngI J Med 320: 627–633, 1989

    Google Scholar 

  18. Sigurdsson H, Baldetorp B, Borg Adalberg 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 

  19. O'Reilly SM, Camplejohn RS, Barnes DMet al.: DNA index, S-phase fraction, histological grade and prognosis in breast cancer. Br J Cancer 61: 671–674, 1990

    Google Scholar 

  20. Gnant MFX, Blijham G, Reiner A, Reiner G, Reynders M, Schutte B, Van Asche C, Steger G, Jakesz R: DNA ploidy and other results of DNA flow cytometry as prognostic factors in operable breast cancer: 10 year results of a randomised study. Eur J Cancer 28: 711–716, 1992

    Google Scholar 

  21. Ewers S-B, Attewell R, Baldetorp B, Borg A, Fernö M, Langström E, Killander D: Prognostic significance of flow cytometric DNA analysis and estrogen receptor content in breast carcinomas - a 10 year survival study. Breast Cancer Res Treat 24: 115–126, 1992

    Google Scholar 

  22. Remvikos Y, Vielh P, Padoy E, Benyahia B, Voillemot N, Magdelénat H: Breast cancer proliferation measured on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation. Br J Cancer 64: 501–507, 1991

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  25. Moran RE, Black MM, Alpert L, Straus MJ: Correlation of cell-cycle kinetics, hormone receptors, histopathology and nodal status in human breast cancer. Cancer 54: 1586–1590, 1984

    Google Scholar 

  26. Kute TE, Muss HB, Hopkins M, Marshall R, Case D, Kammire L: Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer. Breast Cancer Res Treat 6: 113–121, 1985

    Google Scholar 

  27. Horsfall DJ, Tilley WD, Orell SR, Marshall VR, Kant EL: Relationship between ploidy and steroid hormone receptors in primary invasive breast cancer. Br J Cancer 53: 23–28, 1986

    Google Scholar 

  28. Dressler LG, Seamer LC, Owens MA, Clark GM, McGuire WL: DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens. Cancer 61: 420–427, 1988

    Google Scholar 

  29. Feichter GE, Mueller A, Kaufmann Met al.: Correlation of DNA flow cytometric results and other prognostic factors in primary breast cancer. Int J Cancer 823–828, 1988

  30. Muss HM, Kute TE, Case D, Smith R, Booher C, Long R, Kammire L, Gregory B, Brockschmidt JK: The relation of flow cytometry to clinical and biologic characteristics in women with node-negative primary breast cancer. Cancer 64: 1894–1900, 1989

    Google Scholar 

  31. Claus EB, Risch N, Thompson WD: Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48: 232–242, 1991

    Google Scholar 

  32. King M-C: Breast cancer genes: how many, where and who are they? Nature Genetics 2: 89–90, 1992

    Google Scholar 

  33. Beerman H, Kluin PM, Hermans J, Van de Velde CJH, Cornelisse C: Prognostic significance of DNA-ploidy in a series of 690 primary breast cancer patients. Int J Cancer 45: 34–39, 1990

    Google Scholar 

  34. Fernö M, Baldetorp B, Borg A, Olsson H, Sigurdsson H, Killander D: Flow cytometric DNA index and S-phase fraction in breast cancer in relation to other prognostic variables and to clinical outcome. Acta Oncol 31: 157–165, 1992

    Google Scholar 

  35. Joensuu H, Alanen K, Falkmer UG, Klemi P, Nordling S, Remvikos Y, Toikkanen S: Effect of DNA ploidy classification on prognosis in breast cancer. Int J Cancer 52: 701–706, 1992

    Google Scholar 

  36. Kallioniemi OP, Blanco G, Alavaikko M, Hietanen T, Mattila J, Lauslahti K, Lehtinen M, Koivula T: Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction. Cancer 62: 2183–2190, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CNRS URA 620, Institut Curie, 26, rue d'Ulm, 75231, Paris Cedex 05, France

    Yorghos Remvikos & Bernard Dutrillaux

  2. Laboratoire de Radiopathologie, Institut Curie, 26, rue d'Ulm, 75231, Paris Cedex 05, France

    Henri Magdelenat

Authors
  1. Yorghos Remvikos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henri Magdelenat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard Dutrillaux
    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

Remvikos, Y., Magdelenat, H. & Dutrillaux, B. Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis. Breast Cancer Res Tr 34, 25–33 (1995). https://doi.org/10.1007/BF00666488

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00666488

Key words

Search

Navigation