Flow Cytometry in the Management of Breast Cancer

  • H. B. Muss
  • T. E. Kute


There is a pressing need for the further definition of prognostic factors capable of defining the clinical course of patients with primary breast cancer. Current data suggest that approximately 50% of women will present with node-negative (N -) disease, 35% with node-positive (N + ) disease, and 15% with metastases [37]. Of these patients, 25% with N - and 60% with N + will develop locally recurrent or metastatic disease over a 10-year follow-up period. Adjuvant chemotherapy and/or endocrine therapy following primary treatment provides potentially curative treatment for an additional 10%–25% of patients with N+ disease, and current trials suggest benefit in N- patients [35]. For patients with primary operable breast cancer, a continuing clinical dilemma related to the use of adjuvant therapy is the need to treat all patients of a given stage in order to provide effective treatment for only a small proportion of the population. Although tumor size, histologic grade, and steroid receptor status provide information suggesting recurrence risk for large groups of patients, there remains no satisfactory tool for accurate prediction of recurrence in the individual.


Breast Cancer Primary Breast Cancer Steroid Receptor High Proliferative Index Ploidy Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adami HO, Killander D (1984) Prediction of survival in breast cancer - a review. Acta Chir Scand 519: 25–34Google Scholar
  2. 2.
    Auer G, Eriksson E, Azavedo E, Caspersson T, Wallgren A (1984) Prognostic significance of nuclear DNA content in mammary adenocarcinoma in humans. Cancer Res 44: 394–396PubMedGoogle Scholar
  3. 3.
    Azzopardi JP, Chepick OF, Hartmann WH, Jafarey NA, Llombart-Bosch A, Ozzello L, Rilke F, Sassano N, Sobin LH, Sommers SC, Stalsberg H, Sugar J, Williams HO (1982) The World Health Organization histological typing of breast tumors - second edition. Am J Clin Pathol 78: 806–816Google Scholar
  4. 4.
    Baisch H, Goehde W, Linden WA (1985) Analysis of PCP-data to determine the fraction of cells in the various phases of cell cycle. Radiat Environ Biophys 12: 31–39CrossRefGoogle Scholar
  5. 5.
    Barlogie B, Raber MN, Schumann J, Johnson TS, Drewinko B, Swartzendruber DE, Gohde W, Andreeff M, Freireich EJ (1983) Flow cytometry in clinical cancer research. Cancer Res 43: 3982–3997PubMedGoogle Scholar
  6. 6.
    Cornelisse CJ, Moolenaar AJ, Kooyman HJ (1985) Aneuploidy and survival in 566 breast cancer cases. International Conference on Analytical Cytometry XI. Hilton Head, SC, Abst. 340Google Scholar
  7. 7.
    Coulson PB, Thornthwaite JT, Woolley TW, Sugarbaker EV, Seckinger D, (1984) Prognostic indicators including DNA histogram type, receptor content, and staging related to human breast cancer patient survival. Cancer Res 44: 4187–4196PubMedGoogle Scholar
  8. 8.
    Cox DR: (1972) Regression models and life tables (with discussion). J R Stat Soc B 34: 187–220Google Scholar
  9. 9.
    Deshpande N, Mitchell I, Allen D, Morris R (1983) DNA content of carcinomas and prognosis in human breast cancer. Int J Cancer 32: 693–696PubMedCrossRefGoogle Scholar
  10. 10.
    Dressier L, Clark G, Owens M, Pounds G, Oldaker T, McGuire W (1987) DNA flow cytometry predicts for relapse in node negative breast cancer patients. Proc Am Soc Clin Oncol 6:57 (Abst)Google Scholar
  11. 11.
    Ewers SB, Langstrom E, Baldetorp B, Killander D (1984) Flow cytometric DNA analysis in primary breast carcinomas and clinicopathological correlations. Cytometry 5: 408– 419PubMedCrossRefGoogle Scholar
  12. 12.
    Fisher ER, Gregorio RM, Fisher B (1985) The pathology of invasive breast cancer. Cancer 36: 1–85CrossRefGoogle Scholar
  13. 13.
    Fisher B, Fisher ER, Redmond C (1986) Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (l-PAM) in the management of primary breast cancer. J Clin Oncol 4: 929–941PubMedGoogle Scholar
  14. 14.
    Fried J (1976) Method for the quantitative evaluation of data from flow microfluorometry. Comput Biomed Res 9: 263–276PubMedCrossRefGoogle Scholar
  15. 15.
    Fried J, Perez AG, Clarkson BD (1976) Flow cytometric analysis of cell cycle distribution using propidium iodide. J Cell Biol 71: 172–181PubMedCrossRefGoogle Scholar
  16. 16.
    Friedlander ML, Hedley DW, Taylor IW (1984) Clinical and biological significance of aneuploidy in human tumors - a review. J Clin Pathol 37: 961–974PubMedCrossRefGoogle Scholar
  17. 17.
    Hedley DW, Friedlander ML, Taylor IW (1983) Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem 31: 1333–1335PubMedCrossRefGoogle Scholar
  18. 18.
    Hedley DW, Friedlander ML, Taylor IW (1985) Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance. Cytometry 6: 327–333PubMedCrossRefGoogle Scholar
  19. 19.
    Hedley DW, Rugg CA, Gelber RD (1987) Association of DNA index and S-phase fraction with prognosis of nodes positive early breast cancer. Cancer Res 47:4729–4735PubMedGoogle Scholar
  20. 20.
    Kallioniemi O-P, Hietanen T, Mattila J, Lehtinen M, Lauslahti K, Koivula T (1987) 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: 277–282PubMedCrossRefGoogle Scholar
  21. 21.
    Klintenberg C, Stal O, Nordenskjold B, Wallgren A, Arvidsson S, Skoog L (1986) Proliferative index, cytosol estrogen receptor and axillary node status as prognostic predictors in human mammary carcinoma. Breast Cancer Res Treat (Suppl) 7: 99–106Google Scholar
  22. 22.
    Klintenberg C, Wallgren A, Bjelkenkrantz K, Carstenssen J, Humla S, Nordenskjold B, Skoog L et al (1985) DNA distribution, cytosol estrogen receptors and axillary nodes as prognostic predictors in breast cancer. Acta Radiol (Oncol) 24: 253–258CrossRefGoogle Scholar
  23. 23.
    Kute TE, Huske MS, Shore A, Rhyne AL (1980) Improvements in steroid receptor assays including rapid computer analysis of data. Anal Biochem 103: 272–279PubMedCrossRefGoogle Scholar
  24. 24.
    Kute, TE, Muss HB, Hopkins M, Marshall R, Case D, Kammire L (1985) Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer. Breast Cancer Res Treat 6: 113–121PubMedCrossRefGoogle Scholar
  25. 25.
    Masters JR, Camplejohn RS, Millis RR, Rubens RD (1987) Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer. Br J Cancer 55: 455–457PubMedCrossRefGoogle Scholar
  26. 26.
    McDivitt RW, Stone KR, Craig RB, Palmer JO, Meyer JS, Bauer WC (1986) A proposed classification of breast cancer based on kinetic information. Cancer 57: 269–276PubMedCrossRefGoogle Scholar
  27. 27.
    McDivitt RW, Stone KR, Meyer JS (1984) A method for dissociation of viable human breast cancer cells that produces flow cytometric information similar to that obtained by thymidine labeling. Cancer Res 44: 2628–2633PubMedGoogle Scholar
  28. 28.
    Meyer JS, Friedman E, McCrate M, Baur WC (1983) Prediction of early course of breast cancer by thymidine labeling. Cancer 51: 1879–1886PubMedCrossRefGoogle Scholar
  29. 29.
    Meyer JS, Lee JY (1980) Relationship of S-phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival. Cancer Res 40: 1890–1896PubMedGoogle Scholar
  30. 30.
    Mitchell I, Deshpande N, Millis R, Rubins R (1985) Deoxyribonucleic acid (DNA) content of primary carcinoma and response to endocrine or cytotoxic drug therapies in patients with advanced breast cancer. Eur J Surg Oncol 11: 251–256PubMedGoogle Scholar
  31. 31.
    Moran RE, Black MM, Alpert L, Straus MJ (1984) Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer. Cancer 54: 1586–1590PubMedCrossRefGoogle Scholar
  32. 32.
    Muss HB (1984) Principles of cancer chemotherapy; In: Deppe G (ed) Chemotherapy of gynecologic malignancy. Liss, New York, pp 1–30Google Scholar
  33. 33.
    Olszewki W, Darzynkiewicz Z, Rosen PP, Schwartz MD, Meleamed MR (1981) Flow cytometry of breast carcinoma: 1. Relation of DNA ploidy level to histology and estrogen receptor. Cancer 48: 980–984CrossRefGoogle Scholar
  34. 34.
    Owainati AA, Robins RA, Hinton C, Ellis IO, Dowle CS, Ferry B, Elston CW, Blamey RW, Baldwin RW (1987) Tumour aneuploidy, prognostic parameters and survival in primary breast cancer. Br J Cancer 55: 449–454PubMedCrossRefGoogle Scholar
  35. 35.
    Proceedings of the NIH development conference on adjuvant chemotherapy and endocrine therapy for breast cancer. (1986) NCI Monogr 1:1–4Google Scholar
  36. 36.
    Retsky MW, Swartzendruber DE, Wardell RH: (1985) Predicting the disease free survival of breast cancer patients using DNA index and a stochastic numerical model of breast cancer growth. International Conference on Analytical Cytometry XI. Hilton Head, SC, abst 343Google Scholar
  37. 37.
    Silverberg E (1987) Cancer statistics. CA 37: 2–19PubMedGoogle Scholar
  38. 38.
    Silvestrini R, Daidone MG, Costa A, Sanfilippo O (1985) Cell kinetics and in vitro chemosensitivity as a tool for improved management of patients. Eur J Cancer Clin Oncol 21: 371–378PubMedCrossRefGoogle Scholar
  39. 39.
    Silvestrini R, Daidone G, Gasporini G (1985) Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1982–1987PubMedCrossRefGoogle Scholar
  40. 40.
    Stal O, Klintenberg C, Franzen G, Risberg B, Arvidsson S, Bjelken-Krantz K, Skoog L, Nordenskjold B (1986) A comparison of static cytofluorometry and flow cytometry for the estimation of ploidy and DNA-replication in human breast cancer. Breast Cancer Res Treat 7: 15–22PubMedCrossRefGoogle Scholar
  41. 41.
    Taylor IW, Musgrove EA, Friedlander ML, Foo MS, Hedley DW (1983) The influence of age on the DNA ploidy levels of breast cancer. Eur J Cancer Clin Oncol 19: 623–628PubMedCrossRefGoogle Scholar
  42. 42.
    Thornthwaite JT, Sugarbaker EV, Temple WJ (1980) Preparation of tissue for DNA flow cytometric analysis. Cytometry 1: 229–237PubMedCrossRefGoogle Scholar
  43. 43.
    Thorud E, Fossa SD, Vaage S, Kaalhus O, Knudsen OS, Bremer O, Shoaib MC (1986) Primary breast cancer: Flow cytometric DNA pattern in relation to clinical and histopathologic characteristics. Cancer 57: 808–811PubMedCrossRefGoogle Scholar
  44. 44.
    Tubiana M, Pejovic MJ, Renaud A, Contesso G, Chavaudra N, Gioanni J, Malaise EP (1981) Kinetic parameters and the course of the disease in breast cancer. Cancer 47: 937–943PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1989

Authors and Affiliations

  • H. B. Muss
    • 1
  • T. E. Kute
    • 1
  1. 1.Cancer Center of Wake Forest UniversityWinston-SalemUSA

Personalised recommendations