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Nuclear characteristics as indicators of prognosis in node negative breast cancer patients

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Abstract

Nine clinical, biologic and histologic variables were evaluated for their significance in predicting the metastasis free survival (MFS) and the overall survival (OS) of 650 histologic node negative breast cancer patients. The variables studied were: menopausal status, UICC clinical stage of disease, Scarff-Bloom and Richardson (SBR) grade and its 3 components, estrogen and progesterone receptors, and anatomic tumor size. Multivariate Cox analyses revealed that histologic grade and clinical stage were the only significant prognostic factors for both MFS and OS. In the SBR grading system, grades I and III clearly have defined those patients with low and high risk for relapse, respectively. However, it is well known that more than 50% of the patients fall into the intermediate risk category, grade II, which provides essentially no useful prognostic information for those patients. To improve the assignment of patients to specific risk groups, a modified grade (MSBR), with five categories ordered according to the degree of malignancy, has been built from the nuclear pleomorphism and the mitotic index of the SBR grade. In combination with clinical stage, MSBR was found to be a prognostic indicator with high discriminatory power and caused the SBR grade to lose its significance. The first three categories of this MSBR may be gathered to designate low risk patients, whereas the last two categories, once combined, contain all the SBR grade III plus 57% of the SBR grade II tumors, and reliably identify high risk node negative patients. We suggest that a systemic adjuvant therapy should be discussed in this high risk group.

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References

  1. Consensus Conference: Adjuvant chemotherapy for breast cancer. JAMA 254: 3461, 1985

    Google Scholar 

  2. Bonadonna G, Valagussa P, Zambetti M, Buzzoni R, Moliterni A: Milan adjuvant trials for stage I-II breast cancer. In: Salmon SE (ed) Adjuvant Therapy of Cancer V, 211–221. New York: Grune & Stratton, Inc, 1987

    Google Scholar 

  3. Adjuvant tamoxifen in the management of operable breast cancer. The Scottish trial. Lancet 2: 171–175, 1987

    Google Scholar 

  4. NATO (Nolvadex Adjuvant Trial Organization): Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Analysis at 6 years by NATO. Br J Cancer 57: 608–611, 1988

    Google Scholar 

  5. Nissen Meyer R, Host H, Kjellgren K, Mansson B, Morin T: Neoadjuvant chemotherapy in breast cancer as single perioperative treatment and with supplementary long-term chemotherapy. In: Salmon SE (ed) Adjuvant Therapy of Cancer V, 253–261. New York: Grune & Stratton, Inc, 1987

    Google Scholar 

  6. McGuire WL: Estrogen receptor versus nuclear grade as prognostic factors in axillary node negative breast cancer. J Clin Oncol 6: 1071–1072, 1988

    PubMed  Google Scholar 

  7. Parl FF, Schmidt BP, Dupont WD, Wagner RK: Prognostic significance of estrogen receptor status in breast cancer in relation to tumor stage, axillary node metastasis and histopathologic grading. Cancer 54: 2237–2242, 1984

    PubMed  Google Scholar 

  8. Samaan NA, Buzdar AU, Aldinger KA, Schultz PN, Yang KP, Romsdahl MM, Martin R: Estrogen receptor: a prognostic factor in breast cancer. Cancer 47: 554–560, 1981

    PubMed  Google Scholar 

  9. Butler JA, Bretsky S, Menendez Botet C, Kinne DW: Estrogen receptor protein of breast cancer as a predictor of recurrence. Cancer 55: 1178–1181, 1985

    PubMed  Google Scholar 

  10. Fisher B, Redmond C, Fisher ER, Caplan R: Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project protocol B-06. J Clin Oncol 6: 1076–1087, 1988

    PubMed  Google Scholar 

  11. Silvestrini R, Daidone MG, Valagussa P, Salvadori B, Rovini D, Bonadonna G: Cell kinetics as a prognostic marker in locally advanced breast cancer. Cancer Treat Rep 71: 375–379, 1987

    PubMed  Google Scholar 

  12. Tubiana M, Pejovic MJ, Renaud A, Contesso G, Chavaudra N, Gioanni J, Malaise EP: Kinetic parameters and the course of the disease in breast cancer. Cancer 47: 937–943, 1981

    PubMed  Google Scholar 

  13. Harvey J, De Klerk N, Berryman I, Sterrett G, Byrne M, Papadimitriou J: Nuclear DNA content and prognosis in human breast cancer: a static cytophotometric study. Breast Cancer Res Treat 2: 101–110, 1987

    Google Scholar 

  14. Lidereau R, Escot C, Theillet C, Champene MH, Gest J, Brunet M, Callahan R: High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer. JNCI 77: 697–701, 1986

    PubMed  Google Scholar 

  15. Barnard NJ, Hall PA, Lemoine NR, Kadar N: Proliferative index in breast carcinoma determined in situ by Ki67 immuno-staining and its relationship to clinical and pathological variables. J Pathol 152: 287–295, 1987

    PubMed  Google Scholar 

  16. Baak JP, Vandop H, Kurver PH, Hermans J: The value of morphometry to classic prognosticators in breast cancer. Cancer 56: 374–382, 1985

    PubMed  Google Scholar 

  17. Van der Linden HC, Baak JP, Lindeman J, Hermans J, Meyer CJ: Morphometry and breast cancer. II Characterization of breast cancer cells with high malignant potential in patients with spread to lymph nodes: preliminary results. J Clin Pathol 39: 603–609, 1986

    PubMed  Google Scholar 

  18. Ehle BO, Thoresen S, Skjaerven R, Hartveit F: Mean nuclear area and histological grade of axillary-node tumor in breast cancer, related to prognosis. Br J Cancer 46: 95–100, 1982

    PubMed  Google Scholar 

  19. Contesso G, Mouriesse H, Friedman S, Genin J, Sarrazin D, Rouëssé J: The importance of histologic grade in longterm prognosis of breast cancer: a study of 1,010 patients, uniformly treated at the Institut Gustave Roussy. J Clin Oncol 5: 1378–1386, 1987

    PubMed  Google Scholar 

  20. Davis BW, Gelber RD, Goldhirsch A, Hartmann WH, Locher GW, Reed R, Golouh R, Save Soderbergh J, Holloway L, Russell I, Rudenstam CM: Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Cancer 58: 2662–2670, 1986

    PubMed  Google Scholar 

  21. Van de Velde CJH, Gallager HS, Giacco GG: Prognosis in node-negative breast cancer. Breast Cancer Res Treat 8: 189–196, 1986

    PubMed  Google Scholar 

  22. Rank F, Dombernowsky P, Bang Jespersen NC, Vestergaard Pedersen B, Keiding N: Histologic malignancy grading of invasive ductal breast carcinoma. Cancer 60: 1299–1305, 1987

    PubMed  Google Scholar 

  23. Bloom HJ, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–377, 1957

    PubMed  Google Scholar 

  24. Scarff RW, Torloni H: Histological typing of breast tumors. Genève: WHO: 13–20, 1968

    Google Scholar 

  25. Le Doussal V, Tubiana-Hulin M, Friedman S, Hacene K, Spyratos F, Brunet M: Prognostic value of nuclear components of the histologic grade of Scarff-Bloom-Richardson (SBR). A proposed score modification based on a multivariate analysis of 1,262 patients with invasive ductal breast carcinoma. Proc ASCO A: 133, 1988

    Google Scholar 

  26. UICC (International Union Against Cancer): TNM classification of malignant tumors. 3rd Ed, Geneva, UICC 47–54, 1978

    Google Scholar 

  27. Jacquemier J, Vague D, Lieutaud R, De Mascarel I, Trojani M, Le Doussal V et al: Définition et reproductibilité du grading de Scarff et Bloom. In: Evaluation des Moyens de Diagnostic du Cancer du Sein, 173–185. IIIe Journées de la Société Française de Sénologie et de Pathologie Mammaire. Versailles: JMT Conseil, 1981

    Google Scholar 

  28. Vogt Hoerner G, Contesso G: Localisation anatomique du premier ganglion axillaire métastatique du cancer du sein. J Chir (Paris) 86: 37–42, 1963

    Google Scholar 

  29. EORTC (European Organization for Research on Treatment of Cancer): Breast cancer cooperative group. Revision of the standards for the assessment of hormone receptors in human breast cancer. Eur J Cancer 16: 1513–1515, 1980

    Google Scholar 

  30. Kaplan EL, Meier P: Non parametric estimation for incomplete information. J Am Stat Assoc 53: 457–481, 1958

    Google Scholar 

  31. Peto R, Pike MC, Armitage P et al.: Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II Analysis and examples. Br J Cancer 35: 1–39, 1977

    PubMed  Google Scholar 

  32. Cox DR: Regression models and life tables. J R Stat Soc 34: 187–220, 1972

    Google Scholar 

  33. Silvestrini R, Daidone MG, Difronzo G et al.: Prognostic implication of labeling index versus oestrogen receptors and tumor size in node-negative breast cancer. Breast Cancer Res Treat 7: 161–169, 1986

    PubMed  Google Scholar 

  34. Black MM, Opler S, 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, 1955

    PubMed  Google Scholar 

  35. Black MM, Speer FD: Nuclear structure in cancer tissues. Surg Gynecol Obstet 105: 95–102, 1957

    Google Scholar 

  36. Kister SJ, Sommers SG, Haagensen CD et al.: Nuclear grade and sinus histiocytosis in cancer of the breast. Cancer 23: 570–575, 1969

    PubMed  Google Scholar 

  37. Fisher B, Fisher ER, Redmond C et al.: Tumor nuclear grade, estrogen receptor and progesterone receptor, their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer. Breast Cancer Res Treat 7: 147–160, 1986

    PubMed  Google Scholar 

  38. Stenkvist B, Bengtsson E, Eriksson O, Jarkans T, Nordin B, Westman Naeser S: Histopathological systems of breast cancer classification: reproducibility and clinical significance. J Clin Pathol 36: 392–398, 1983

    PubMed  Google Scholar 

  39. Henson DE: The histological grading of neoplasms. Arch Pathol Lab Med 112: 1091–1096, 1988

    PubMed  Google Scholar 

  40. Rosen PP, Saigo PE, Braun DW, Weathers E, De Palo A: Predictors of recurrence in stage I (T1N0M0) breast carcinoma. Ann Surg: 15–25, 1981

  41. Haybittle JL, Blamey RW, Elston CW, Johnson J, Doyle PJ, Campbell FC, Nicholson RI, Griffiths K: A prognostic index in primary breast cancer. Br J Cancer 45: 361–366, 1982

    PubMed  Google Scholar 

  42. Nealon TF, Nkongho A, Grossi C, Gillooley J: Pathologic identification of poor prognosis stage I (T1N0M0) cancer of the breast. Ann Surg 190: 129–132, 1979

    PubMed  Google Scholar 

  43. Fisher B, Redmond C, Fisher ER, Bauer M, Wolmark N, Wickerham DL, Deutsch M, Montague E, Margolese R, Foster R: Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 312: 674–681, 1985

    PubMed  Google Scholar 

  44. Levitt SH, Mandel J: Benefits versus risks in conservation surgery with irradiation for breast cancer. Am J Med 77: 93–100, 1983

    Google Scholar 

  45. Floiras JL, Guerin P, Hacene K, Leducq J, Pallud C, Brunet M, Gest J: Perisurgical adjuvant chemotherapy of breast cancer with one short course of thiotepa. Preliminary results. Breast Dis-Senol 1: 27–34, 1985

    Google Scholar 

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Authors and Affiliations

  1. From the Department of Pathology, Centre Anticancéreux René Huguenin, St Cloud, France

    V. le Doussal

  2. From the Department of Medicine, Centre Anticancéreux René Huguenin, St Cloud, France

    M. Tubiana-Hulin & S. Friedman

  3. From the Department of Statistics, Centre Anticancéreux René Huguenin, St Cloud, France

    K. Hacene & M. Brunet

Authors
  1. V. le Doussal
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  2. M. Tubiana-Hulin
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  3. K. Hacene
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  4. S. Friedman
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  5. M. Brunet
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le Doussal, V., Tubiana-Hulin, M., Hacene, K. et al. Nuclear characteristics as indicators of prognosis in node negative breast cancer patients. Breast Cancer Res Tr 14, 207–216 (1989). https://doi.org/10.1007/BF01810737

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