Cancer Immunology, Immunotherapy

, Volume 37, Issue 3, pp 209–212 | Cite as

In vivo modulation of natural killer cell activity by tamoxifen in patients with bilateral primary breast cancer

  • E. Robinson
  • D. Rubin
  • T. Mekori
  • R. Segal
  • S. Pollack
Original Articles NK Activity, Tamoxifen, Breast Cancer, Multiple Primary Neoplasms


Natural killer (NK) cell activity, the autologous mixed lymphocyte reaction (AMLR) and proportions of T cell subpopulations (CD3+/CD4+ and CD3+/CD8+) and NK cells (CD16+) were studied in 21 patients with bilateral primary breast cancer (BBC), 10 patients with single-breast cancer (SBC) and 20 healthy controls. All patients studied had no evidence of disease and had been off radiotherapy and/or chemotherapy for at least 1 year. Ten patients with BBC were also treated with tamoxifen. Patients with SBC had NK cell activity, AMLR responses and T cell subpopulations that were comparable to those of normal controls. In patients with BBC, a significant (P<0.01) increase in NK activity compared to that in normal controls (42±13% versus 21±10%, effector-to-target cell ratio, 25∶1) and a significant (P<0.05) decrease in CD4+ T cell proportions (30±15% versus 49±13%) and absolute numbers (472±82/mm3 versus 953±131/mm3) were found. However, the proliferative response of BBC patients' T lymphocytes in AMLR was in the range of the normal controls. Lymphocytes derived from 10 BBC patients treated with tamoxifen exhibited NK cell activity that was comparable to that of normal controls and patients with SBC, and was significantly (P<0.01) reduced compared to the pretreatment period. BBC patients who received tamoxifen also show a reduction in the proportion of CD4+ T cells and in AMLR proliferative responses, which decreased compared to levels in normal controls. Taken together, these results indicate that long-term tamoxifen treatment modulates immune responses in BBC patients.

Key words

NK activity Tamoxifen Breast cancer Multiple primary neoplasms 


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  1. 1.
    Berry J, Green BJ, Matheson DS (1987) Modulation of natural killer cell activity by tamoxifen in stage I post-menopause breast cancer. Eur J Cancer Clin Oncol 23: 517PubMedGoogle Scholar
  2. 2.
    Bonilla F, Alvares-Mon M, Merino P, Giron JA, Mendez SR, Espana P, Durantez A (1990) Natural killer activity in patients with breast cancer. Eur J Gynaecol Oncol 11: 103PubMedGoogle Scholar
  3. 3.
    Brenner BG, Friedman G, Margolese RG (1985) The relationship of clinical status and therapeutic modality to NK cell activity in human breast cancer. Cancer 56: 1543PubMedGoogle Scholar
  4. 4.
    Cannon NE, Bonnard G, Ojen W, Herberman R (1977) Relationship of human natural lymphocyte mediated cytotoxicity of breast cancer derived target cells. Int J Cancer 19: 487PubMedGoogle Scholar
  5. 5.
    Cunningham-Rundles S, Filippa DA, Braun DW, Antonelli P, Ashikori F (1981) Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women. JNCI 67: 585PubMedGoogle Scholar
  6. 6.
    Editorial (1988) Second primary breast cancer. Br Med J 296: 1755Google Scholar
  7. 7.
    Ermin O, Ashby J, Stephens J (1978) Human natural cytotoxicity in the blood and lymph organs of healthy donors and patients with malignant diseases. Int J Cancer 21: 35PubMedGoogle Scholar
  8. 8.
    Friedman-Birnbaum R, Weltfriend S, Pollack S (1991) Classic Kaposi sarcoma: T lymphocyte subsets and NK cell activity. J Am Acad Dermatol 24: 937PubMedGoogle Scholar
  9. 9.
    Harvey EB, Brinton LA (1985) Second cancer following cancer of the breast in Connecticut, 1935–82. NCI Monogr 68: 99Google Scholar
  10. 10.
    Henderson JC (1987) Adjuvant systemic therapy for early breast cancer. Curr Probl Cancer 11: 125PubMedGoogle Scholar
  11. 11.
    Joensun H, Toivanen A, Nordman E (1986) Effect of tamoxifen on immune functions. Cancer Treat Rep 70: 381PubMedGoogle Scholar
  12. 12.
    Mackay IR, Googjear MDE, Riglar C, Penschow J (1983) Effect of natural killer antibody dependent cellular cytotoxicity of adjuvant cytostatic chemotherapy including melphalan in breast cancer. Cancer Immunnol Immunother 16: 98Google Scholar
  13. 13.
    Myers MJ, Butler LD, Petersen BH (1986) Estradiol-induced alteration in the immune system. II. Suppression of cellular immunity in the rat is not the result of direct estrogenic action. Immunopharmacology 11: 47PubMedGoogle Scholar
  14. 14.
    Nolvadex Adjuvant Trial Organization (1987) Controlled trial of tamoxifen as single adjuvant agent in the management of early breast cancer: analysis of six years. Lancet I: 836Google Scholar
  15. 15.
    Robinson E, Mekori T, Segal R, Nasarllah S (1993) The T helper and suppressor lymphocyte subset in patients with multiple primary cancers. Oncology (in press)Google Scholar
  16. 16.
    Romain PL, Lipsky PE (1983) Immunoglobulin secretion during the autologous mixed lymphocyte reaction in man. J Immunol 130: 1146PubMedGoogle Scholar
  17. 17.
    Rotstein S, Blomgren H, Petrini B, Wasserman J, Von Steding LV (1988) Influence of adjuvant tamoxifen on blood lymphocytes. Breast Cancer Res Treat 12: 75PubMedGoogle Scholar
  18. 18.
    Rouse BT, Horohov DW (1986) Immunosuppression in viral infections. Rev Infect Dis 8: 850PubMedGoogle Scholar
  19. 19.
    Sheard CR, Reiley F, Tee DEH, Vergani D, Lowe D, Baum M, Cameron AEP (1986) The effect of adjuvant cyclophosphamide and tamoxifen on the number of lymphocytes bearing T cells or NK cells. Br J Cancer 54: 705PubMedGoogle Scholar
  20. 20.
    Tartter PI, Steinberg B, Barron D, Martinelli G (1987) The prognostic significance of natural killer cytotoxicity in patients with colorectal cancer. Arch Surg 122: 1264PubMedGoogle Scholar
  21. 21.
    Toncini G, Barni S, Rescaldani R (1990) Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms. Oncology 47: 381PubMedGoogle Scholar
  22. 22.
    Webster DJT, Richardson G, et al (1979) Effect of treatment on the immunological status of women with advanced breast cancer. Br J Cancer 39: 676PubMedGoogle Scholar
  23. 23.
    White D, Jone DB, Cooke T, Kirham N (1982) Natural killer activity in peripheral blood lymphocytes of patients with benign and malignant disease. Br J Cancer 46: 611PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • E. Robinson
    • 1
  • D. Rubin
    • 2
  • T. Mekori
    • 1
  • R. Segal
    • 1
  • S. Pollack
    • 2
  1. 1.Faculty of Medicine-TechnionNorthern Israel Oncology CenterHaifaIsrael
  2. 2.Division of Clinical Immunology and AllergyRambam Medical CenterHaifaIsrael

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