Advertisement

Breast Cancer Research and Treatment

, Volume 15, Issue 3, pp 149–160 | Cite as

Cytometric and histopathologic features of tumors detected in a randomized mammography screening program: Correlation and relative prognostic influence

  • T. Hatschek
  • O. Gröntoft
  • G. Fagerberg
  • O. Stål
  • S. Sullivan
  • J. Carstensen
  • B. Nordenskjöld
Report

Summary

Cytometric determination of S-phase fraction and ploidy type was performed on 430 tumors detected within a randomized trial of mammographic screening. The results were compared to several histopathologic features. A high S-phase fraction was estimated in tumors with a high grade of malignancy and other histopathologic findings related to rapid tumor progression, including lack of tubule formation, a high mitotic index, marked nuclear pleomorphism, multifocal cancer growth, tumor emboli in lymphatic and blood vessels, tumor necrosis, and inflammatory reaction. DNA aneuploidy was correlated with a high malignancy grade, frequent mitoses, a high degree of nuclear pleomorphism, vascular invasion, necrosis, and the presence of noninvasive ductal carcinoma. Both cytometric variables were inversely related to the degree of elastosis. Positive nodes, large tumor size, DNA aneuploidy, a high S-phase fraction, high grade of malignancy, lack of tubule formation, as well as high mitotic index and pleomorphism, presence of multifocal cancer, and vascular invasion, predicted a significantly shorter distant recurrence-free interval after a median follow-up time of 46.6 months. Elastosis and the presence of estrogen and progesterone receptors indicated favorable prognosis. In the multivariate analysis, only lymph node status, tumor size S-phase fraction, and multifocal growth pattern had independent prognostic value.

Key words

breast cancer cytometry histopathology mammography prognosis screening 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Scarff RW, Torloni H: Histological typing of breast tumours. World Health Organization, Geneva, 1968Google Scholar
  2. 2.
    Black MM, Opler SR, Speer FD: Survival in breast cancer cases in relation to the structure of the primary tumor and regional lymph nodes. Surg Gynecol Obstet 100: 543–551, 1955PubMedGoogle Scholar
  3. 3.
    Cornelisse CJ, van de Velde CJH, Caspers RJC, Moolenaar AJ, Hermans J: DNA ploidy and survival in breast cancer patients. Cytometry 8: 225–234, 1987PubMedGoogle Scholar
  4. 4.
    Harvey J, de Klerk N, Berryman I, Sterett G, Byrne M, Papadimitriou J: Nuclear DNA content and prognosis in human breast cancer: a static cytophotometric study. Breast Cancer Res Treat 9: 101–109, 1987PubMedGoogle Scholar
  5. 5.
    Hedley DW, Rugg CA, Gelber RD: Association of DNA index and S-phase fraction with prognosis of nodes positive early breast cancer. Cancer Res 47: 4729–4735, 1987PubMedGoogle Scholar
  6. 6.
    Kallioniemi OP, Hietanen T, Mattila J, Lehtinen M, Lauslahti K, Koivula T: Aneuploid DNA content and high Sphase fraction of tumour cells are related to poor prognosis in patients with primary breast cancer. Eur J Cancer Clin Oncol 23: 277–282, 1987PubMedGoogle Scholar
  7. 7.
    Klintenberg C, Stål O, Nordenskjöld B, Wallgren A, Arvidsson S, Skoog L: Proliferative index, cytosol estrogen receptor, and axillary node status as prognostic predictors in human mammary carcinoma. Breast Cancer Res Treat 7: 99–106, 1986Google Scholar
  8. 8.
    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 320: 627–633, 1989PubMedGoogle Scholar
  9. 9.
    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, 1988PubMedGoogle Scholar
  10. 10.
    Meyer JS, Friedman E, McCrate MM, Bauer WC: Prediction of early course of breast carcinoma by thymidine labelling. Cancer 51: 1879–1886, 1983PubMedGoogle Scholar
  11. 11.
    Meyer JS, Prey MU, Babcock DS, McDivitt RW: Breast carcinoma cell kinetics morphology, stage, and host characteristics. Lab Invest 54: 41–51, 1986PubMedGoogle Scholar
  12. 12.
    McDivitt RW, Stone KR, Craig RB, Palmer JO, Meyer JS, Bauer WC: A proposed classification of breast cancer based on kinetic information. Cancer 57: 269–276, 1986PubMedGoogle Scholar
  13. 13.
    Hatschek T, Fagerberg G, Stål O, Sullivan S, Carstensen J, Gröntoft O, Nordenskjöld B: Cytometric characterization and clinical course of breast cancer diagnosed in a population based screening program. Cancer 64: 1074–1081, 1989PubMedGoogle Scholar
  14. 14.
    Gröntoft O: Staging and grading of invasive ductal carcinoma in a randomized population screened by mammography: the first and second screens. In: Day NE, Miller AB (eds) Screening for Breast Cancer. Hans Huber Publishers, Toronto, 1988, pp 79–82Google Scholar
  15. 15.
    Fagerberg G, Baldetorp L, Gröntoft O, Lundström B, Månsson JC, Nordenskjöld B: Effects of repeated mammographic screening on breast cancer stage distribution. Acta Radiol Oncol 24: 465–472, 1985PubMedGoogle Scholar
  16. 16.
    World Health Organization: Histological typing of breast tumours (rev ed). Geneva, 1981Google Scholar
  17. 17.
    Bergman C, Gröntoft O, Olofsson J, Risberg B: A technique for whole-organ sectioning and its applications. Science Tools 27: 46–50, 1980Google Scholar
  18. 18.
    Azzopardi JG: Cancerization of lobules. In: Azzopardi JG (ed) Problems in Breast Pathology. W.B. Saunders Company Ltd, London, 1979, pp 203–213Google Scholar
  19. 19.
    Risberg B, Stål O, Bjelkenkrantz K, Hatschek T, Franzén G, Arvidsson S, Nordenskjöld B: Use of formalin fixed, paraffin embedded tumours for estimation of cellular DNA content and S-phase fraction by static cytofluorometry. Acta Radiol Oncol 24: 537–544, 1985PubMedGoogle Scholar
  20. 20.
    Bjelkenkrantz K, Stål O, Gröntoft O: A fast and reliable system for microcomputerized DNA cytofluorometry in tumour pathology. Histochem 79: 145–155, 1983Google Scholar
  21. 21.
    Wrange Ö, Nordenskjöld B, Gustafsson JÅ: Cytosol estradiol receptor in human mammary carcinoma: an assay based on isoelectric focusing in polyacrylamide gel. Anal Biochem 85: 461–475, 1978PubMedGoogle Scholar
  22. 22.
    Wrange Ö, Humla S, Ramberg I, Gustafsson SA, Skoog L, Nordenskjöld B, Gustafsson JÅ: Progestin-receptor analysis in human breast cancer cytosol by isoelectric focusing in slabs of polyacrylamide gel. J Steroid Biochem 14: 141–148, 1981PubMedGoogle Scholar
  23. 23.
    Armitage P, Berry G: Statistical Methods in Medical Research. Blackwell Scientific Publications, Oxford 1987Google Scholar
  24. 24.
    Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K: Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35: 1–39, 1977PubMedGoogle Scholar
  25. 25.
    Kaplan E, Meier P: Nonparametric estimation from incomplete observations. J Amer Statist Assoc 53: 457–481, 1958Google Scholar
  26. 26.
    Cox DR: Regression models and life tables. J R Statist Soc B 34: 187–220, 1972Google Scholar
  27. 27.
    Dowle CS, Owainati A, Robins A, Burns K, Ellis IO, Elston CW, Blamey RW: Prognostic significance of the DNA content of human breast cancer. Br J Surg 74: 133–136, 1987PubMedGoogle Scholar
  28. 28.
    Héry M, Gioanni J, Lalanne CM, Namer M, Courdi A: The DNA labelling index: a prognostic factor in node-negative breast cancer. Breast Cancer Res Treat 9: 207–211, 1987PubMedGoogle Scholar
  29. 29.
    Silvestrini R, Daidone MG, Gasparini G: Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1982–1987, 1985PubMedGoogle Scholar
  30. 30.
    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 33: 441–445, 1984PubMedGoogle Scholar
  31. 31.
    Wallgren A, Silfverswärd C, Eklund G: Prognostic factors in mammary carcinoma. Acta Radiol 15: 1–16, 1976Google Scholar
  32. 32.
    Rank F, Dombernowsky P, Jespersen NCB, Pedersen BV, Keiding N: Histologic malignancy grading of invasive ductal breast carcinoma. Cancer 60: 1299–1305, 1987PubMedGoogle Scholar
  33. 33.
    Fisher ER, Gregorio RM, Fisher B, Redmond C, Vellios F, Sommers SC: The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (Protocol No. 4). Cancer 36: 1–85, 1975PubMedGoogle Scholar
  34. 34.
    Carter D, Pipkin RD, Shepard RH, Elkins RC, Abbey H: Relationship of necrosis and tumor border to lymph node metastases and 10-year survival in carcinoma of the breast. Am J Surg Pathol 2: 39–46, 1978PubMedGoogle Scholar
  35. 35.
    Gump FE, Shikora S, Habif DV, Kister S, Logerfo P, Estabrook A: The extent and distribution of cancer in breasts with palpable primary tumors. Ann Surg 204: 384–390, 1986PubMedGoogle Scholar
  36. 36.
    van de Velde CJH, Gallager HS, Giacco GG: Prognosis in node negative breast cancer. Breast Cancer Res Treat 8: 189–196, 1986PubMedGoogle Scholar
  37. 37.
    Sampat MB, Sirsat MV, Gangadharan P: Prognostic significance of blood vessel invasion in carcinoma of the breast in women. J Surg Oncol 9: 623–632, 1977PubMedGoogle Scholar
  38. 38.
    Davis BW, Gelber R, Goldhirsch A, Hartmann WH, Hollaway L, Russell I, Rudenstam CM: Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Hum Pathol 16: 1212–1218, 1985PubMedGoogle Scholar
  39. 39.
    Mate TP, Carter D, Fischer DB, Hartman PV, McKhann C, Merino M, Prosnitz LR, Weissberg JB: A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma. Cancer 58: 1995–2002, 1986PubMedGoogle Scholar
  40. 40.
    Parham DM, Robertson AJ, Brown RA: Morphometric analysis of breast carcinoma: association and survival. J Clin Pathol 41: 173–177, 1988PubMedGoogle Scholar
  41. 41.
    Fisher ER, Sass R, Fisher B, Gregorio R, Brown R, Wickerham L: Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol 6). II. Relation of local breast recurrence to multicentricity. Cancer 57: 1717–1724, 1986PubMedGoogle Scholar
  42. 42.
    Humeniuk V, Forrest APM, Hawkins RA, Prescott R: Elastosis and primary breast cancer. Cancer 52: 1448–1452, 1983PubMedGoogle Scholar
  43. 43.
    Millis RR: Correlation of hormone receptors with pathological features in human breast cancer. Cancer 46: 2869–2871, 1980PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • T. Hatschek
    • 1
  • O. Gröntoft
    • 2
  • G. Fagerberg
    • 3
  • O. Stål
    • 1
  • S. Sullivan
    • 1
  • J. Carstensen
    • 1
  • B. Nordenskjöld
    • 1
  1. 1.Department of OncologyUniversity HospitalLinköpingSweden
  2. 2.Department of PathologyUniversity HospitalLinköpingSweden
  3. 3.Department of Diagnostic RadiologyUniversity HospitalLinköpingSweden

Personalised recommendations