The Immunology and Molecular Biology of Breast Cancer

  • Isha A. Mustafa
  • Kirby I. Bland


Though often overlooked, the breast functions as part of the immune system. Normal breast tissue contains not only glandular epithelial cells, adipocytes and blood vessels, but also lymphocytes. There are cells of immune origin present within the breast at all times which continuously release IgA [1]. Additionally, immunoglobulin and possibly T-cell immunity is passed from mother to infant during the time of lactation [2].


Breast Cancer Cytokine Profile Factor Vascular Endothelial Cell Growth Breast Cancer Therapy Tumoricidal Activity 
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  1. 1.
    Going JJ, Anderson TJ, Battersby S, MacIntyre CCA. Proliferative and secretory activity in human breast during natural and artificial menstrual cycles. Am J Pathol 1988;130:152–63.Google Scholar
  2. 2.
    Eglinton BA, Roberton DM, Cummings AG. Phenotype of T-cells, their soluble receptor levels, and cytokine profile of human breast milk. Immunol Cell Biol 1994;72:306–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Black MM, Leis HP. Cellular responses to autologous breast cancer tissue. Sequential observations. Cancer, 1973;32:384–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Vose BM, Moore M. Suppressor cell activity of lymphocytes infiltrating human lung and breast tumours. Int J Cancer 1979;24:579–85.PubMedCrossRefGoogle Scholar
  5. 5.
    Eremin O, Coombs RRJ, Ashby. Lymphocytes infiltrating human breast cancers lack K-cell activity and show low levels of NK-cell activity. Br J Cancer 1981;44:166–76.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Whiteside TL, Miescher S, Hurlimann J, Moretta L, von Fliedner V. Clonal analysis and in situ characterization of lymphocytes infiltrating human breast carcinomas. Cancer Immunol Immunother 1986;23:169–78.PubMedCrossRefGoogle Scholar
  7. 7.
    Wong PY, Staren ED, Tereshkova N, Braun DP. Functional analysis of tumor-infiltrating leukocytes in breast cancer patients. J Surg Res 1998;76:95–103.PubMedCrossRefGoogle Scholar
  8. 8.
    Vanky F, Wang P, Patarroyo M, Klein E. Expression of the adhesion molecule ICAM-l and major histocompatability complex class I antigens on human tumor cells is required for their interactions with autologous lymphocytes in vitro. Cancer Immunol Immunother 1990;31:19–27.PubMedCrossRefGoogle Scholar
  9. 9.
    Ogmundsdottir HM, Petursdottir I and Gudmundsdottir I. Interactions between the immune system and breast cancer. Acta Oncologica 1995;34(5):647–50.PubMedCrossRefGoogle Scholar
  10. 10.
    Black MM, Zachrau RE, Hankey BF, Feuer EJ. Prognostic significance of in situ carcinoma associated with invasive breast carcinoma. Cancer 1996;78:778–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Bankfalvi A, Terpe H-J, Breukelmann D, Bier B, Rempe D, Pschadka G, Krech R and Bocker W. Gains and Losses of CD44 expression during breast carcinogenesis. Histopathology 1998;33:107–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Lippman ME, Dickson RB. Mechanisms of growth control in normal and malignant breast epithelium. Recent Prog Horm Res 1989;45:383–440.PubMedGoogle Scholar
  13. 13.
    Toi M, Bicknell R, Harris AL. Inhibition of colon and breast carcinoma cell growth by IL-4. Cancer Res 1992;52:275–9.PubMedGoogle Scholar
  14. 14.
    Benaud C, Dickson RB, Thompson EW. Roles of the matrix metalloproteinases in mammary gland development and cancer. Breast Ca Res Treat 1998;50(2):97–116.CrossRefGoogle Scholar
  15. 15.
    Wang M, Liu YE, Greene J, Sheng S, Fuchs A, Rosen EM, et al. Metalloproteinase inhibitors to treat cancer progresssion. Oncogene 1997;14(23):2767–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Sporn MB, Roberts AB. Peptide growth factors and inflammation, tissue repair and cancer. J Clin Invest 1986;78:329–32.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Brown DC, Purushotham AD, Birnie GD, George WD. Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction. Surgery 1995;117:96–101.CrossRefGoogle Scholar
  18. 18.
    Reid SE, Scanlon EF, Murthy MS. Do blood-borne cancer cells contribute to local recurrence? Clin Exp Metastasis 1994;12:91.Google Scholar
  19. 19.
    Mayhew E, Glaves D. Quantitation of tumorigenic disseminating and arrested cancer cells. Br J Cancer 1984;50:159–66.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Fisher B, Bauer M, Margolese R et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985;312:665–73.PubMedCrossRefGoogle Scholar
  21. 21.
    Fisher B, Redmond C, Poisson R, et al. Eight year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Holland R, Veling SH, Mravunac M, Hendriks JHCL. Histologic multifocality of Tis and T1–2 breast carcinomas. Implications for clinial trials of breast-conserving surgery. Cancer 1985;56:979–90.PubMedCrossRefGoogle Scholar
  23. 23.
    Clark RM, McCulloch PB, Levine MN, et al. Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 1992;84:683–89.PubMedCrossRefGoogle Scholar
  24. 24.
    Clarke DH, Martinez AA. Identification of patients who are at high risk for locoregional breast cancer recurrence after conservative surgery and radiotherapy: a review article for surgeons, pathologists, and radiation and medical oncologists. J Clin Oncol 1992;10:474–83.PubMedGoogle Scholar
  25. 25.
    Kurtz JM. Factors influencing the risk of local recurrence in the breast. Eur J Cancer 1992;28:660–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Relf M, LeJeune S, Scott PAE et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor b-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to antiogenesis. Cancer Res 1997;57:963–9.PubMedGoogle Scholar
  27. 27.
    Reid SE, Scanlon EF, Kaufman MW, Murthy MS. Role of cytokines and growth factors in promoting the local recurrence of breast cancer. Br J Surgery 1996;83:313–20.CrossRefGoogle Scholar
  28. 28.
    Radinsky R, Fidler IJ. Regulation of tumor cell growth at organ-specific metastases. In Vivo 1992;6:325–31.PubMedGoogle Scholar
  29. 29.
    Smith RR, Thomas LB, Hilberg AW. Cancer cell contamination of operative wounds. Cancer 1958;11:53–62.PubMedCrossRefGoogle Scholar
  30. 30.
    Murphy P, Alexander P, Senior PV, Fleming J, Kirkham N, Taylor I. Mechanisms of organ selective tumour growth by bloodborne cancer cells. Br J Cancer 1988;57:19–31.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Davies DE, Farmer S, White J, Senior P, Warnes S, Alexander P. Contribution of host-derived growth factors to in vivo growth of a transplantable murine mammary carcinoma. Br J Cancer 1994;70:263–9.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Baker DG, Masterson TM, Pace R, Constable WC, Wanebo H. The influence of the surgical wound on local tumor recurrence. Surgery 1989;106:525–32.PubMedGoogle Scholar
  33. 33.
    Murthy MS, Goldschmidt RA, Rao LN, Ammirati M, Buchmann T, Scanlon EF. The influence of surgical trauma on experimental metastases. Cancer 1989;64:2035–44.PubMedCrossRefGoogle Scholar
  34. 34.
    Simpson-Herren L, Sanford AH, Holmquist JP. Effects of surgery on the cell kinetics of residual tumor. Cancer Tret Rep 1976;60:1749–60.Google Scholar
  35. 35.
    Gunduz N, Fisher B, Saffer EA. Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res 1979;39:3861–5.PubMedGoogle Scholar
  36. 36.
    Yamamura M, Modlin RL, Ohmen JD, Moy RL. Local expression of antiinflammatory cytokines in cancer. J Clin Invest 1993;91:1005–10.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Venetsanakos E, Beckman I, Bradley J, Skinner JM. High incidence of interleukin 10mRNA but not interleukin 2 mRNA detected in human breast tumours. Br J Cancer 1997;75(12):1826–30.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Becker JC, Brabletz T, Czerny C, Termeer C, Brocker EB. Tumour escape mechanisms from immunosurveillance: induction of unresponsiveness in a specific MNC-restricted CD4+ human T cell clone by the autologous MHC class II+ melanoma. Int Immunol 1993;5:1501–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Becker JC, Czerny C, Brocker EB. Maintenance of clonal anergy by endogenously produced IL-10. Int Immunol, 1994:6:1605–12.PubMedCrossRefGoogle Scholar
  40. 40.
    Coventry BJ, Weeks SC, Heckford SE, Sykes PJ Bradley J, Skinner JM. Lack of IL-2 Cytokine expression despite IL-2 messenger RNA transcription in tumor-infiltrating lymphocytes in primary human breast carcinoma. J Immun 1996;156:3486–92.PubMedGoogle Scholar
  41. 41.
    Golumbek, PT, Lazemby AJ, Levitsky HJ, Jaffee LM, Karusuyama H, Baker M, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 1991;254:713–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Lorenzen J, Lewis CE, McCracken D, Horak E, Greenal M, McGee JOD. Human tumor-associated NK cells secrete increased amounts of interferon-gamma and interleukin-4. Br J Cancer 1991;64:457–62.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Kaklamanis L, Koukourakis MI, Leek R, Giatromanolaki A, Ritter M, Whitehouse R, et al. Loss of interleukin 4 receptor-associated molecule gp200-MR6 in human breast cancer: prognostic significance. Br J Cancer 1996;74:1627–31.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Tuttle TM, Anderson BW, Thompson WE, et al. Proliferative and cytokine responses to class II HER-2/neu-associated peptides in breast cancer patients. Clin Ca Res 1998;4:2015–24.Google Scholar
  45. 45.
    Cobleigh MA. Efficacy and safety of Herceptin (humanized anti-HER2 antibody) as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc Mer Soc Clin Oncol 1998;17:97a (abstract #376).Google Scholar
  46. 46.
    Slamon D. Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER2+/MBC) markedly increases anti-cancer activity: A randomized multinational controlled phase III trial. Proc Amer Soc Clin Oncol 1998;17:98a (abstract #377).Google Scholar
  47. 47.
    Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene, 1999 Apr 1;18(13):2241–51.PubMedCrossRefGoogle Scholar
  48. 48.
    Dougall WC, Greene MI. Biological studies and potential therapeutic applications of monoclonal antibodies and small molecules reactive with the neu/c-erbB-2 protein. Cell Biophys 1994;24–25:209–18.Google Scholar
  49. 49.
    Katsumata M, Okudaira T, Samanta A, Clark DP, Drebin JA, Jokicoeur P, et al. Prevention of breast tumour development in vivo by downregulation of the p185neu receptor. Nat Med 1995;1(7):644–8.PubMedCrossRefGoogle Scholar

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© Springer-Verlag London 2002

Authors and Affiliations

  • Isha A. Mustafa
  • Kirby I. Bland

There are no affiliations available

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