Abstract
Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
Similar content being viewed by others
References
Elston CW: Grading of invasive carcinoma of the breast. In: Page DL, Anderson TJ (eds) Diagnostic Histopathology of the Breast. Churchill Livingstone, Edinburgh, 1987, pp 300-311
von Hanseman D: Uber assymmetrische Zelltheilung in Epitelkrebsen und deren biologische Beduetung. Virchows Arch A Pathol Pathol Anat 119: 229-326, 1890
Baldetorp B, Bendahl PO, Ferno M, Alanen K, Delle U, Falkmer U, Hansson-Aggesjo B, Hockenstrom T, Lindgren A, Mossberg L: Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of 12 laboratories' results for 67 sample homogenates. Cytometry 22: 115-127, 1995
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, 1994
Bergers E, Montironi R, van Diest PJ, Prete E, Baak JP: Interlaboratory reproducibility of semiautomated cell cycle analysis of flow cytometry DNA-histograms obtained from fresh material of 1, 295 breast cancer cases. Hum Pathol 27: 553-560, 1996
Dettmar P, Harbeck N, Thomssen C, Pache L, Ziffer P, Fizi K, Janicke F, Nathrath W, Schmitt M, Graeff H, Hofler H: Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer. Br J Cancer 75: 1525-1533, 1997
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19: 403-410, 1991
Ferno 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
Fisher ER: Prognostic and therapeutic significance of pathological features of breast cancer. NCI Monogr 29-34, 1986
Frierson HF Jr, Wilbur DC, Gaffey MJ, Salmon I, Franquemont DW, Berean KW, Wolber RA, Kiss R: Quantitative image cytometry of infiltrating ductal carcinoma: comparison with prognostic parameters and reproducibility of histological grade. Hum Pathol 27: 821-826, 1996
Frierson HF Jr, Wolber RA, Berean KW, Franquemont DW, Gaffey MJ, Boyd JC, Wilbur DC: Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol 103: 195-198, 1995
Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 22: 207-219, 1992
Hatschek T, Grontoft O, Fagerberg G, Stal O, Sullivan S, Carstensen J, Nordenskjold B: Cytometric and histopathologic features of tumors detected in a randomized mammography screening program: correlation and relative prognostic influence. Breast Cancer Res Treat 15: 149-160, 1990
Leonardi E, Cristofori A, Caffo O, Dalla Palma P: Cytometric DNA analysis and prognostic biomarkers in breast carcinoma. Expression of P53 product in the different ploidy classes. Anal Cell Pathol 15: 31-45, 1997
Neville AM, Bettelheim R, Gelber RD, Save-Soderbergh J, Davis BW, Reed R, Torhorst J, Golouh R, Peterson HF, Price KN: Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group. J Clin Oncol 10: 696-705, 1992
Pfisterer J, Kommoss F, Sauerbrei W, Menzel D, Kiechle M, Giese E, Hilgarth M, Pfleiderer A: DNA flow cytometry in node-positive breast cancer. Prognostic value and correlation with morphologic and clinical factors. Anal Quant Cytol Histol 17: 406-412, 1995
Pinder SE, Murray S, Ellis IO, Trihia H, Elston CW, Gelber RD, Goldhirsch A, Lindtner J, Cortes-Funes H, Simoncini E, Byrne MJ, Golouh R, Rudenstam CM, Castiglione-Gertsch M, Gusterson BA: The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 83: 1529-1539, 1998
Remvikos Y, Mosseri V, Asselain B, Fourquet A, Durand JC, Pouillart P, Magdelenat H: S-phase fractions of breast cancer predict overall and post-relapse survival. Eur J Cancer 33: 581-586, 1997
Risberg B, Baldetorp B, Ferno M, Hansson B, Mossberg LL, Roos G, Stal O, Thornthwaite JT, Tibell L: Inter-institutional reproducibility of flow cytometric DNA-analysis in breast carcinomas. Anal Cell Pathol 6: 23-36, 1994
Robbins P, Pinder S, de Klerk N, Dawkins H, Harvey J, Sterrett G, Ellis I, Elston C: Histological grading of breast carcinomas: a study of introbserver agreement. Hum Pathol 26: 873-879, 1995
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
Sigurdsson H, Baldetorp B, Borg A, Dalberg M, Ferno M, Killander D, Olsson H, Ranstam J: Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels. Br J Cancer 62: 786-790, 1990
Stal O, Brisfors A, Carstensen J, Ferraud L, Hatschek T, Nordenskjold B: Relationships of DNA ploidy, S-phase fraction and hormone receptor status to tumor stage in breast cancers detected by population screening. The South-East Sweden Breast Cancer Group. Int J Cancer 51: 28-33, 1992
Stal O, Dufmats M, Hatschek T, Carstensen J, Klintenberg C, Rutqvist LE, Skoog L, Sullivan S, Wingren S, Nordenskjold B: S-phase fraction is a prognostic factor in stage I breast carcinoma. J Clin Oncol 11: 1717-1722, 1993
Stal O, Skoog L, Rutqvist LE, Carstensen JM, Wingren S, Sullivan S, Andersson AC, Dufmats M, Nordenskjold B: S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer. Br J Cancer 70: 1258-1262, 1994
Stal O, Wingren S, 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
Stat Soft I: Computer Program Manual. Stat Soft, Tulsa, OK, 1995
Sundquist M, Thorstenson S, Brudin L, Nordenskjöld B: Applying the Nottingham Prognostic Index to a Swedish breast cancer population. Breast Cancer Res Treat 53: 1-8, 1999
Vindelov L, Christensen I, Nissen N: A detergent-trypsin method for the preparation for flow cytometric DNA analysis. Cytometry 3: 323-327, 1983
Wersto RP, Stetler-Stevenson M: Debris compensation of DNA histograms and its effect on S-phase analysis. Cytometry 20: 43-52, 1995
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sundquist, M., Thorstenson, S., Brudin, L. et al. A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer. Breast Cancer Res Treat 63, 11–15 (2000). https://doi.org/10.1023/A:1006494625644
Issue Date:
DOI: https://doi.org/10.1023/A:1006494625644