Journal of Mammary Gland Biology and Neoplasia

, Volume 6, Issue 4, pp 375–392 | Cite as

Prognostic Factors in Breast Cancer: Current and New Predictors of Metastasis

  • Daniel F. Hayes
  • Claudine Isaacs
  • Vered Stearns


Decisions regarding the use of adjuvant therapy for breast cancer are strongly influenced by the risk of disease recurrence and death. These risks are now determined by examining the currently recognized breast cancer prognostic factors, including clinical stage, axillary nodal status, tumor size and grade, hormone receptor status, and presence of lymphovascular involvement. Newer factors are being evaluated in an attempt to more precisely define disease-related prognosis. This paper provides an overview of issues that need to be considered when analyzing studies of prognostic factors as well as a review of the currently recognized and the newer candidate prognostic factors.

breast cancer prognostic factors adjuvant systemic therapy tumor marker utility grading system 


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  1. 1.
    S. Nass, I. C. Henderson, and J. C. Lashoff (2001). Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer, National Academy Press, Washington, DC.Google Scholar
  2. 2.
    Early Breast Cancer Trialist's Collaborative Group (1998). Polychemotherapy for early breast cancer: An overview of the randomized trials. Lancet 352:930-942.Google Scholar
  3. 3.
    Early Breast Cancer Trialist's Collaborative Group (1998). Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 351:1451-1467.Google Scholar
  4. 4.
    Early Breast Cancer Trialists Collaborative Group (1996). Ovarian ablation in early breast cancer: Overview of the randomised trials. Lancet 348:1189-1196.Google Scholar
  5. 5.
    Early Breast Cancer Trialists' Collaborative Group (2000). Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 355:1757-1770.Google Scholar
  6. 6.
    R. Peto, J. Boreham, M. Clarke, C. Davies, and V. Beral (2000). UK and USA breast cancer deaths down 25% in year 2000 at ages 20-69 years. Lancet 355:1822.Google Scholar
  7. 7.
    W. S. Halsted (1894-95). The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Johns Hopkins Hosp. Rep. iv:297-350.Google Scholar
  8. 8.
    American Joint Committee on Cancer (1997). In I. Fleming, J. Cooper, D. Henson, R. Hutter, B. J. Kennedy, G. Murphy, B. O'Sullivan, L. Sobin, and J. Yarbro (eds.), AJCC Cancer Staging Handbook, Breast, 5th edn., Vol. 1, Lippincott-Raven, Philadelphia, pp. 171-180.Google Scholar
  9. 9.
    D. F. Hayes, R. Bast, C. E. Desch, H. Fritsche, N. E. Kemeny, J. Jessup, G. Y. Locker, J. Macdonald, R.G. Mennel, L. Norton, P. Ravdin, S. Taube, and R. Winn (1996). Atumor marker utility grading system (TMUGS): A framework to evaluate clinical utility of tumor markers. J. Natl. Cancer Inst. 88:1456-1466.Google Scholar
  10. 10.
    R. Simon and D. G. Altman (1994). Statistical aspects of prognostic factor studies in oncology. Br. J. Cancer 69:979-985.Google Scholar
  11. 11.
    D. G. Altman and G. H. Lyman (1998). Methodological challenges in the evaluation of prognostic factors in breast cancer. Breast Cancer Res. Treat. 52:289-303.Google Scholar
  12. 12.
    W. L. McGuire (1991). Breast cancer prognostic factors: Evaluation guidelines. J. Natl. Cancer Inst. 83:154-155.Google Scholar
  13. 13.
    G. Gasparini, F. Pozza, and A. L. Harris (1993). Evaluating the potential usefulness ofnewprognostic and predictive indicators in node-negative breast cancer patients. J. Natl. Cancer Inst. 85:1206-1219.Google Scholar
  14. 14.
    D. F. Hayes, B. Trock, and A. Harris (1998). Assessing the clinical impact of prognostic factors: When is “statistically significant” clinically useful? Breast Cancer Res. Treat. 52:305-319.Google Scholar
  15. 15.
    W. L. McGuire and G. M. Clark (1992). Prognostic factors and treatment decisions in axillary-node-negative breast cancer. N. Engl. J. Med. 326:1756-1761.Google Scholar
  16. 16.
    G. Gasparini (1998). Prognostic variables in node-negative and node-positive breast cancer [editorial]. Breast Cancer Res. Treat. 52:321-331.Google Scholar
  17. 17.
    ASCO Expert Panel (1996). Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer: Report of the american society of clinical oncology expert panel. J. Clin. Oncol. 14:2843-2877.Google Scholar
  18. 18.
    ASCO Expert Panel (1998). 1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. J. Clin. Oncol. 16:793-795.Google Scholar
  19. 19.
    R. C. Bast Jr., P. Ravdin, D. F. Hayes, S. Bates, H. Fritsche Jr., J. M. Jessup, N. Kemeny, G. Y. Locker, R. G. Mennel, and M. R. Somerfield (2001). 2000 Update of recommendations for the use of tumor markers in breast and colorectal cancer: Clinical practice guidelines of the american society of clinical oncology. J. Clin. Oncol. 19:1865-1878.Google Scholar
  20. 20.
    C. Isaacs, V. Stearns, and D. F. Hayes (2001). New prognostic factors for breast cancer recurrence. Semin. Oncol. 28:53-67.Google Scholar
  21. 21.
    P. Ravdin, I. Siminoff, and J. Harvey (1998). Survey of breast cancer patients concerning their knowledge and expectations of adjuvant therapy. J. Clin. Oncol. 16:515-521.Google Scholar
  22. 22.
    A. S. Coates and R. J. Simes (1992). Patient Assessment of Adjuvant Treatment in Operable Breast Cancer, Wiley, New York.Google Scholar
  23. 23.
    C. Lindley, S. Vasa, T. Sawyer, and E. Winer (1998). Quality of life and preferences for treatment following systemic adjuvant therapy for early stage breast cancer. J. Clin. Oncol. 16:1380-1387.Google Scholar
  24. 24.
    S. Rajagopal, P. J. Goodman, and I. F. Tannock (1994). Adjuvant chemotherapy for breast cancer: Discordance between physicians' perception of benefit and the results of clinical trials. J. Clin. Oncol. 12:1296-1304.Google Scholar
  25. 25.
    P. M. Ravdin, L. A. Siminoff, G. J. Davis, M. B. Mercer, J. Hewlett, N. Gerson, and H. L. Parker (2001). Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J. Clin. Oncol. 19:980-991.Google Scholar
  26. 26.
    I. C. Henderson, D. Berry, G. Demetri, C. Cirrincione, L. Goldstein, S. Martino, J. Ingle, M. Cooper, G. Canellos, E. Borden, G. Fleming, J. Holland, S. Graziano, J. Carpenter, H. Muss, and L. Norton (1998). Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer. Proc. Am. Soc. Clin. Oncol. 17:101a.Google Scholar
  27. 27.
    C. L. Carter, C. Allen, and D. E. Henson (1989). Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63:181-187.Google Scholar
  28. 28.
    P. P. Rosen, S. Groshen, D. W. Kinne, and L. Norton (1993). Factors influencing prognosis in node-negative breast carcinoma: Analysis of 767 T1N0M0/T2N0M0 patients with longterm follow-up. J. Clin. Oncol. 11:2090-2100.Google Scholar
  29. 29.
    C. A. Quiet, D. J. Ferguson, R. R. Weichselbaum, and S. Hellman (1995). Natural history of node-negative breast cancer: A study of 826 patients with long-term follow-up. J. Clin. Oncol. 13:1144-1151.Google Scholar
  30. 30.
    J. F. Simpson and D. L. Page (1994). Status of breast cancer prognostication based on histopathologic data. Am. J. Clin. Pathol. 102:S3-S8.Google Scholar
  31. 31.
    P. P. Rosen, S. Groshen, P. E. Saigo, D.W. Kinne, and S. Hellman (1989). Pathological prognostic factors in Stage I (T1N0M0) and Stage II (T1N1M0) breast carcinoma: A study of 644 patients with median follow-up of 18 years. J. Clin. Oncol. 7:1239-1251.Google Scholar
  32. 32.
    H. J. Bloom and W.W. Richardson (1957). Histological grading and prognosis in breast cancer. Br. J. Cancer 11:359-377.Google Scholar
  33. 33.
    C. W. Elston and I. O. Ellis (1991). Pathological prognostic factors in breast cancer. 1. The value of histological gade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 19:403-409.Google Scholar
  34. 34.
    B. Fisher, C. Redmond, E. R. Fisher, and R. Caplan (1988). 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.Google Scholar
  35. 35.
    G. Contesso, H. Mouriesse, S. Friedman, J. Genin, D. Sarrazin, and J. Rouesse (1987). The importance of histologic grade in long-term prognosis of breast cancer:Astudy of 1,010 patients, uniformly treated at the Institut Gustave-Roussy. J. Clin. Oncol. 5:1378-1386.Google Scholar
  36. 36.
    J. W. Yarbro, D. L. Page, L. P. Fielding, E. E. Partridge, and G. P. Murphy (1999). American Joint Committee on Cancer prognostic factors consensus conference. Cancer 86:2436-2446.Google Scholar
  37. 37.
    P. L. Fitzgibbons, D. L. Page, D. Weaver, A. D. Thor, D.C. Allred, G. M. Clark, S.G. Ruby, F. O'Malley, J. F. Simpson, J. L. Connolly, D. F. Hayes, S. B. Edge, A. Lichter, and S. J. Schnitt (2000). Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch. Pathol. Lab. Med. 124:966-978.Google Scholar
  38. 38.
    K. Gilchrest, L. Kalish, V. Gould, H. S. J. Imbriglia, W. Levy, A. Patchefsky, D. Penner, J. Pickren, J. Roth, R. Schinella, I. Schwartz, and J. Wheeler (1985). Interobserver reproducibility of histopathological features in stage II breast cancer. Breast Cancer Res. Treat. 5:3-10.Google Scholar
  39. 39.
    L. W. Dalton, S. E. Pinder, C. E. Elston, I. O. Ellis, D. L. Page, W. D. Dupont, and R.W. Blamey (2000). Histologic grading of breast cancer: Linkage of patient outcome with level of pathologist agreement. Mod. Pathol. 13:730-735.Google Scholar
  40. 40.
    D. L. Page, W. D. Dupont, R. A. Jensen, and J. F. Simpson (1998). When and to what end do pathologists agree? J. Natl. Cancer Inst. 90:88-89.Google Scholar
  41. 41.
    A. M. Neville, R. Bettelheim, R.D. Gelber, J. Save-Soderbergh, B. W. Davis, R. Reed, J. Torhorst, R. Golouh, H. F. Peterson, K. N. Price, et al. (1992). Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group. J. Clin. Oncol. 10:696-705.Google Scholar
  42. 42.
    W. L. McGuire, A. K. Tandon, D. C. Allred, G. C. Chamness, and G. M. Clark (1990). How to use prognostic factors in axillary node-negative breast cancer patients. J. Natl. Cancer Inst. 82:1006-1015.Google Scholar
  43. 43.
    S.G. Hilsenbeck, P. M. Ravdin, C. A. de Moor, G. C. Chamness, C. K. Osborne, and G. M. Clark (1998). Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res. Treat. 52:227-237.Google Scholar
  44. 44.
    C. R. Wenger and G. M. Clark (1998). S-phase fraction and breast cancer-a decade of experience. Breast Cancer Res. Treat. 51:255-265.Google Scholar
  45. 45.
    L. Hutchins, S. Green, P. Ravdin, D. Lew, S. Martino, M. Abeloff, A. Lyss, I. C. Henderson, C. Allred, S. Dakhil, L. Pierce, W. Goodwin, J. Caton, S. Rivkin, R. Chapman, and K. Osborne (1998). CMF vs. CAF with and without tamoxifen in high-risk node-negataive breast cancer patients and a natural history follow-up study in low-risk node-negative patients: First results of intergroup trial INT0102. Proc. Am. Soc. Clin. Oncol. 17:1a.Google Scholar
  46. 46.
    R. W. Brown, C. D. Allred, G. M. Clark, C. K. Osborne, and S.G. Hilsenbeck (1996). Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer. Clin. Cancer Res. 2:585-592.Google Scholar
  47. 47.
    A. D. Thor, S. Liu, D. H. Moore II, and S. M. Edgerton (1999). Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J. Clin. Oncol. 17:470-477.Google Scholar
  48. 48.
    D. Amadori and R. Silvestrini (1998). Prognostic and predictive value of thymidine labelling index in breast cancer. Breast Cancer Res. Treat. 51:267-281.Google Scholar
  49. 49.
    L. Dressler, K. Conway, J. Geradts, S. Edminston, D. Cowan, M. Burroughs, L. Cui, M. He, J. Pang, K. Mistry, S. Drouin, Y. Li, J. Tse, R. Millikan, and B. Newman (1999). Immunohistochemistry can accurately detect missense mutations in the p53 gene:Acomparison with gene sequencing in 196 breast cancers. Proc. Am. Assoc. Cancer Res. 40:690a.Google Scholar
  50. 50.
    C. MacGeoch, G. Turner, L. Bobrow, D.M. Barnes, D. Bishop, and N. Spurr (1995). Heterogeneity in Li-Fraumeni families: p53 mutation analysis and immunohistochemical staining. J. Med. Genet. 32:186-190.Google Scholar
  51. 51.
    P. D. Pharoah, N. E. Day, and C. Caldas (1999). Somatic mutations in the p53 gene and prognosis in breast cancer: A metaanalysis. Br. J. Cancer 80:1968-1973.Google Scholar
  52. 52.
    J. Reed (1994). Bcl-2 and the regulaton of programmed cell death. J. Cell Biol. 124:1-6.Google Scholar
  53. 53.
    S. Krajewski, A. Thor, S. Edgerton, D. Moore, M. Krajewska, and J. Reed (1997). Analysis of bax and bcl-2 in p53-immunopositive breast cancers. Clin. Cancer Res. 3:199-208.Google Scholar
  54. 54.
    S. Krajewski, C. Blomqvist, K. Franssila, M. Krajewska, V. M. Wasenius, E. Niskanen, S. Nordling, and J.C. Reed (1995). Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res. 55:4471-4478.Google Scholar
  55. 55.
    O. I. Olopade, M. O. Adeyanju, A. R. Safa, F. Hagos, R. Mick, C. B. Thompson, and W. M. Recant (1997). Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J. Sci. Am. 3:230-237.Google Scholar
  56. 56.
    C. Gillett, P. Smith, W. Gregory, M. Richards, R. Millis, G. Peters, and D. Barnes (1996). Cyclin D1 and prognosis in human breast cancer. Int. J. Cancer 69:92-99.Google Scholar
  57. 57.
    D. M. Barnes and C. E. Gillett (1998). Cyclin D1 in breast cancer. Breast Cancer Res. Treat. 52:1-15.Google Scholar
  58. 58.
    R. Seshadri, C. S. Lee, R. Hui, K. McCaul, D. J. Horsfall, and R. L. Sutherland (1996). Cyclin DI amplification is not associated with reduced overall survival in primary breast cancer but may predict early relapse in patients with features of good prognosis. Clin. Cancer Res. 2:1177-1184.Google Scholar
  59. 59.
    A. L. Schechter, D. F. Stern, L. Vaidyanathan, S. J. Decker, J. A. Drebin, M. I. Greene, and R. A. Weinberg (1984). The neu oncogene: An erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312:513-516.Google Scholar
  60. 60.
    D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich, and W. L. McGuire (1987). Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177-182.Google Scholar
  61. 61.
    B. J. Trock, H. Yamauchi, M. Brotzman, V. Stearns, and D. F. Hayes (2000). c-erbB-2 as a prognostic factor in breast cancer: A meta-analysis. Proc. Am. Soc. Clin. Oncol. 19:97a.Google Scholar
  62. 62.
    H. Yamauchi, V. Stearns, and D. F. Hayes (2001). When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J. Clin. Oncol. 19:2334-2356.Google Scholar
  63. 63.
    M.F. Press, L. Bernstein, P. A. Thomas, L.F. Meisner, J.Y. Zhou, Y. Ma, G. Hung, R. A. Robinson, C. Harris, A. El-Naggar, D. J. Slamon, R. N. Phillips, J. S. Ross, S. R. Wolman, and K. J. Flom (1997). HER-2/neu gene amplification characterized by fluorescence in situ hybridization: Poor prognosis in node-negative breast carcinomas. J. Clin. Oncol. 15:2894-2904.Google Scholar
  64. 64.
    K. Siziopikou, S. Schnitt, J. Connolly, and D. F. Hayes (1999). Detection and significance of occult axillary metastatic disease in breast cancer patients. Breast J. 5:221-229.Google Scholar
  65. 65.
    D. Krag, D. Weaver, T. Ashikaga, F. Moffat, V. S. Klimberg, C. Shriver, S. Feldman, R. Kusminsky, M. Gadd, J. Kuhn, S. Harlow, and P. Beitsch (1998). The sentinel node in breast cancer-a multicenter validation study. N. Engl. J. Med. 339:941-946.Google Scholar
  66. 66.
    A. E. Giuliano, R.C. Jones, M. Brennan, and R. Statman (1997). Sentinel lymphadenectomy in breast cancer. J. Clin. Oncol. 15:2345-2350.Google Scholar
  67. 67.
    N. Hansen, B. J. Grube, W. Te, M. L. Brennan, R. Turner, and A. E. Giuliano (2001). Clinical significance of axillary micrometastases in breast cancer: How small is too small. Proc. Am. Soc. Clin. Oncol. 20:223a.Google Scholar
  68. 68.
    I. Funke and W. Schraut (1998). Meta-analyses of studies on bone marrow micrometastases:Anindependent prognostic impact remains to be substantiated. J. Clin. Oncol. 16:557-566.Google Scholar
  69. 69.
    I. J. Diel, M. Kaufmann, S. D. Costa, R. Holle, G. von Minckwitz, E. F. Solomayer, S. Kaul, and G. Bastert (1996). Micrometastatic breast cancer cells in bone marrow at primary surgery: Prognostic value in comparison with nodal status. J. Natl. Cancer Inst. 88:1652-1658.Google Scholar
  70. 70.
    S. Braun, K. Pantel, P. Muller, W. Janni, F. Hepp, C. R. Kentenich, S. Gastroph, A. Wischnik, T. Dimpfl, G. Kindermann, G. Riethmuller, and G. Schlimok (2000). Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N. Engl. J. Med. 342:525-533.Google Scholar
  71. 71.
    G. Gebauer, T. Fehm, E. Merkle, E. P. Beck, N. Lang, and W. Jager (2001). Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: Clinical outcome during long-term follow-up. J. Clin. Oncol. 19:3669-3674.Google Scholar
  72. 72.
    J. Folkman (1990).What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. 82:4-6.Google Scholar
  73. 73.
    N. Weidner, J. Folkman, F. Pozza, P. Bevilacqua, E. Allred, S. Meli, and G. Gasparini (1992). Tumor angiogenesis: A new significant and independent prognostic indicator in early stage breast carcinoma. J. Natl. Cancer Inst. 84:1875-1887.Google Scholar
  74. 74.
    G. Gasparini (2001). Clinical significance of determination of surrogate markers of angiogenesis in breast cancer. Crit. Rev. Oncol. Hematol. 37:97-114.Google Scholar
  75. 75.
    A. J. Guidi, D. Berry, G. Broadwater, B. Helmchen, I. Bleiweiss, D. Budman, I. C. Henderson, L. Norton, and D. F. Hayes (submitted). Association ofangiogenesis and disease outcome in node-positive breast cancer patients treated with adjuvantCAF chemotherapy: A CALGB correlative science study from protocols 8541/8869. J. Clin. Oncol. 20:732-742.Google Scholar
  76. 76.
    G. Gasparini, M. Toi, M. Gion, P. Verderio, R. Dittadi, M. Hanatani, I. Matsubara, O. Vinante, E. Bonoldi, P. Boracchi, C. Gatti, H. Suzuki, and T. Tominaga (1997). Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J. Natl. Cancer Inst. 89:139-147.Google Scholar
  77. 77.
    U. Eppenberger, W. Kueng, J. M. Schlaeppi, J. L. Roesel, C. Benz, H. Mueller, A. Matter, M. Zuber, K. Luescher, M. Litschgi, M. Schmitt, J. A. Foekens, and S. Eppenberger-Castori (1998). Markers of tumor angiogenesis and proteolysis independently define high-and low-risk subsets of nodenegative breast cancer patients. J. Clin. Oncol. 16:3129-3136.Google Scholar
  78. 78.
    B. R. Westley and F. E. May (1996). Cathepsin D and breast cancer. Eur. J. Cancer 32A:15-24.Google Scholar
  79. 79.
    P. M. Ravdin, C. A. de Moor, S.G. Hilsenbeck, M. K. Samoszuk, P. M. Vendely, and G. M. Clark (1997). Lack of prognostic value of cathepsin D levels for predicting short term outcomes of breast cancer patients. Cancer Lett. 116:177-183.Google Scholar
  80. 80.
    G. Ferrandina, G. Scambia, F. Bardelli, P. Benedetti Panici, S. Mancuso, and A. Messori (1997). Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: A meta-analysis. Br. J. Cancer 76:661-666.Google Scholar
  81. 81.
    R.W. Stephens, N. Brunner, F. Janicke, and M. Schmitt (1998). The urokinase plasminogen activator system as a target for prognostic studies in breast cancer. Breast Cancer Res. Treat. 52:99-111.Google Scholar
  82. 82.
    J. A. Foekens, H. A. Peters, M. P. Look, H. Portengen, M. Schmitt, M.D. Kramer, N. Brunner, F. Janicke, M.E. Meijervan Gelder, S. C. Henzen-Logmans, W. L. van Putten, and J. G. Klijn (2000). The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res. 60:636-643.Google Scholar
  83. 83.
    F. Janicke, A. Prechtl, C. Thomssen, N. Harbeck, C. Meisner, M. Untch, C. G. Sweep, H. K. Selbmann, H. Graeff, and M. Schmitt (2001). Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J. Natl. Cancer Inst. 93:913-920.Google Scholar
  84. 84.
    D. W. Visscher, F. Sarkar, P. LoRusso, W. Sakr, S. Ottosen, S. Wykes, and J.D. Crissman (1993). Immunohistologic evaluation of invasion-associated proteases in breast carcinoma. Mod. Pathol. 6:302-306.Google Scholar
  85. 85.
    A. B. Tuck, F. P. O'Malley, H. Singhal, J. F. Harris, K. S. Tonkin, N. Kerkvliet, Z. Saad, G. S. Doig, and A. F. Chambers (1998). Osteopontin expression in a group of lymph node negative breast cancer patients. Int. J. Cancer 79:502-508.Google Scholar
  86. 86.
    R. Heimann and S. Hellman (2000). Individual characterisation of the metastatic capacity of human breast carcinoma. Eur. J. Cancer 36:1631-1639.Google Scholar
  87. 87.
    R. Heimann, F. Lan, R. McBride, and S. Hellman (2000). Separating favorable from unfavorable prognostic markers in breast cancer: The role of E-cadherin. Cancer Res. 60:298-304.Google Scholar
  88. 88.
    R. Heimann, D. J. Ferguson, and S. Hellman (1998). The relationship between nm23, angiogenesis, and the metastatic proclivity of node-negative breast cancer. Cancer Res. 58:2766-2771.Google Scholar
  89. 89.
    H. Yu, M. A. Levesque, G. M. Clark, and E. P. Diamandis (1999). Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. Br. J. Cancer 81:490-495.Google Scholar
  90. 90.
    A. Remacle, K. McCarthy, A. Noel, T. Maguire, E. McDermott, N. O'Higgins, J.M. Foidart, and M. J. Duffy (2000). High levels of TIMP-2 correlate with adverse prognosis in breast cancer. Int. J. Cancer 89:118-121.Google Scholar
  91. 91.
    T. Ueno, M. Toi, M. Koike, S. Nakamura, and T. Tominaga (2000). Tissue factor expression in breast cancer tissues: Its correlation with prognosis and plasma concentration. Br. J. Cancer 83:164-170.Google Scholar
  92. 92.
    R. Yoshida, N. Kimura, Y. Harada, and N. Ohuchi (2001). The loss of E-cadherin, alpha-and beta-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer. Int. J. Oncol. 18:513-520.Google Scholar
  93. 93.
    M. Emi, M. Yoshimoto, T. Sato, S. Matsumoto, Y. Utada, I. Ito, K. Minobe, T. Iwase, T. Katagiri, K. Bando, F. Akiyama, Y. Harada, K. Fukino, G. Sakamoto, M. Matsushima, A. Iida, T. Tada, H. Saito, Y. Miki, F. Kasumi, and Y. Nakamura (1999). Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 correlates with poor postoperative prognosis in breast cancer. Genes Chromosomes Cancer 26:134-141.Google Scholar
  94. 94.
    Y. Utada, M. Emi, M. Yoshimoto, F. Kasumi, F. Akiyama, G. Sakamoto, S. Haga, T. Kajiwara, and Y. Nakamura (2000). Allelic loss at 1p34-36 predicts poor prognosis in node-negative breast cancer. Clin. Cancer Res. 6:3193-3198.Google Scholar
  95. 95.
    R. Hui, R. D. Macmillan, F. S. Kenny, E. A. Musgrove, R. W. Blamey, R. I. Nicholson, J. F. Robertson, and R. L. Sutherland (2000). INK4a gene expression and methylation in primary breast cancer: Overexpression of p16INK4a messenger RNA is a marker of poor prognosis. Clin. Cancer Res. 6:2777-2787.Google Scholar
  96. 96.
    X. Yang, L. Yan, and N. E. Davidson (2001). DNAmethylation in breast cancer. Endocr. Relat. Cancer 8:115-127.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Daniel F. Hayes
    • 1
  • Claudine Isaacs
    • 2
  • Vered Stearns
    • 1
  1. 1.Breast Oncology ProgramUniversity of Michigan Comprehensive Cancer CenterAnn Arbor
  2. 2.Breast Cancer Program, Lombardi Cancer CenterGeorgetown UniversityWashington

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