Summary
Several potential prognostic factors are available today for patients with breast cancer, and many more are being identified and studied. To evaluate the clinical utility of these factors, it will be necessary to measure them on a large number of patients, and then follow these patients so that multivariate survival analyses can be performed.
The Oncology Research Network was established in 1986 by the University of Texas Health Science Center at San Antonio and Nichols Institute Reference Laboratories in order to evaluate the clinical utility of new prognostic factors for patients with primary breast cancer. The first generation of prognostic factors included steroid receptors, along with DNA ploidy and S-phase fraction determined by flow cytometry. Currently, laboratory results have been obtained from more than 127,000 patients, and follow-up information is available on a subset of more than 25,000 of these patients.
S-phase fraction was related to the ploidy status of the tumor. An increased incidence of aneuploidy and higher S-phase fractions were found in estrogen and progesterone receptor negative tumors, tumors from patients with positive axillary lymph nodes, tumors greater than 2 cm in diameter, and patients younger than 35 years of age. Preliminary survival analyses suggest that S-phase fraction and DNA ploidy, in combination with other prognostic factors, are powerful predictors of early disease relapse.
The Oncology Research Network provides an important resource for examining the clinical significance of new laboratory assays and for expediting improvements in existing laboratory techniques.
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References
McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM: How to use prognostic factors in axillary nodenegative breast cancer patients. J Natl Cancer Inst 82: 1006–1015, 1990
McGuire WL, Dressler LG: Emerging impact of flow cytometry in predicting recurrence and survival in breast cancer patients. J Natl Cancer Inst 75: 405–410, 1985
Merkel DE, McGuire WL: Ploidy, proliferative activity and prognosis. DNA flow cytometry of solid tumors. Cancer 65: 1194–1205, 1990
Bichel P, Poulsen S, Anderson J: Estrogen receptor content and ploidy in human mammary carcinoma. Cancer 50: 1771–1774, 1982
Ewers S-B, Langstrom E, Baldetorp B, Killander D: Flowcytometric DNA analysis in primary breast carcinomas and clinicopathological correlations. Cytometry 5: 408–419, 1984
Moran R, Black M, Alpert L: Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer. Cancer 54: 1586–1590, 1984
McDivitt RW, Stone KR, Cragi RB, Palmer JG, Meyer JS, Bauer WC: A proposed classification of breast cancer based on kinetic information: derived from a comparison of risk factors in 168 primary operable breast cancers. Cancer 57: 269–276, 1986
Thorud E, Fossa SD, Vaage S, Kaalhus O, Knudsen OS, Bormer O, Shoaib MC: Primary breast cancer: Flow cytometric DNA pattern in relation to clinical and histopathological characteristics. Cancer 57: 808–811, 1986
Kallioniemi O-P, Blanco G, Alavaikko M, Hietanen T, Mattila J, Lauslahti K, Koivula T: Tumour DNA ploidy as an independent prognostic factor in breast cancer. Br J Cancer 56: 637–642, 1987
Hedley DW, Rugg CA, Gelber RD: Association of DNA index and S-phase fraction with prognosis of node positive early breast cancer. Cancer Res 47: 4729–4735, 1987
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
Lykkesfeldt AE, Balslev I, Christensen IJ, Larsen JK, Molgaard H, Rasmussen BB, Thorpe S, Rose C: DNA ploidy and S-phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease. Acta Oncol 27: 749–756, 1988
Muss HB, Kute TE, Case LD, Smith LR, Booher C, Long R, Kammire L, Gregory B, Brockschmidt JK: The relation of flow cytometry to clinical and biological characteristics in women with node negative primary breast cancer. Cancer 64: 1894–1900, 1989
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, 1989
Helin HJ, Helle MJ, Kallioniemi OP, Isola JJ: Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and DNA flow cytometry. Cancer 63: 1761–1767, 1989
Christov K, Miley A, Todorov V: DNA aneuploidy and cell proliferation in breast tumors. Cancer 65: 673–679, 1989
Kallioniemi O-P, 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. A proposed classification of DNA histograms in breast cancer. Cancer 62: 2183–2190, 1988
Winchester DJ, Duda RB, August CZ, Goldschmidt RA, Wruck DM, Rademaker AW, Winchester DP, Merkel DE: The importance of DNA flow cytometry in node-negative breast cancer. Arch Surg 125: 886–889, 1990
Visscher DW, Zarbo RJ, Jacobsen G, Kambouris A, Talpos G, Sakr W: Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations. Lab Invest 62: 370–378, 1990
Keyhani-Rofagha S, O'Toole RV, Farrar WB, Sickle-Santanello B, DeCenzo J, Young D: Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma? Cancer 65: 1577–1582, 1990
Kute TE, Muss HB, Cooper MR, Case LD, Buss D, Stanley V, Gregory B, Galleshaw J, Bocher K: The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients. Cancer 66: 1810–1816, 1990
Vielh P, Chevillard S, Mosseri V, Donatini B, Magdelenat H: Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. Am J Clin Path 94: 681–686, 1990
Joensuu H, Toikkanen S, Klemi PJ: DNA index and S-phase fraction and their combination as prognostic factors in operable ductal breast carcinoma. Cancer 66: 331–340, 1990
Lewis WE: Prognostic significance of flow cytometric DNA analysis in node-negative breast cancer patients. Cancer 65: 2315–2320, 1990
Sigurdsson H, Baldetorp B, Borg A, Dalberg M, Ferno M, Killander D, Olsson H: Indicators of prognosis in node-negative breast cancer. N Engl J Med 322: 1045–1053, 1990
Cornelisse CJ, van de Velde CJH, Caspers RJC, Moolenaar AJ, Hermans J: DNA ploidy and survival in breast cancer patients. Cytometry 8: 225–234, 1987
Dressler LG, Seamer L, Owens MA, Clark GM, McGuire WL: Evaluation of a modeling system for S-phase estimation in breast cancer by flow cytometry. Cancer Res 47: 5294–5302, 1987
Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malley BW, McGuire WL: Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res 51: 105–109, 1991
Olsson H, Ranstam J, Baldetorp B, Ewers S-B, Ferno M, Killander D, Sigurdsson H: Proliferation and DNA ploidy in malignant breast tumors in relation to early oral contraceptive use and early abortions. Cancer 67: 1285–1290, 1991
Horsfall DJ, Tilley MD, Orell SR, Marshall VE, McKant EL: Relationship between ploidy and steroid hormone receptors in primary invasive breast cancer. Br J Cancer 53: 23–28, 1986
Uyterlinde AM, Schipper NW, Baak JP: Comparison of extent of disease and morphometric and DNA flow cytometric prognostic factors in invasive ductal breast cancer. J Clin Pathol 40: 1432–1436, 1987
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We regret to report that Dr. William L. McGuire died on March 25, 1992, after this work was largely completed
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Wenger, C.R., Beardslee, S., Owens, M.A. et al. DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients. Breast Cancer Res Tr 28, 9–20 (1993). https://doi.org/10.1007/BF00666351
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DOI: https://doi.org/10.1007/BF00666351