Tamoxifen as an Immunomodulating Agent
The nonsteroidal antiestrogenic agent, tamoxifen (TX), has gained wide therapeutic application for the treatment of breast carcinomas and of some other sex hormone dependent tumors.1 Numerous investigations indicate that TX is capable of combining with the estrogen receptor of tumor cells which results in partial activation of the receptor, but without the growth promoting effect of estradiol (E2), which is the proper ligand for the receptor. For this reason TX and related drugs (ethamoxytriphethol or MER25, and clomiphene) are referred to under the collective term, nonsteroidal antiestrogens. 2 However, it was also demonstrated that nonsteroidal antiestrogens are able to inhibit the stimulatory effect of growth factors, such as epidermal growth factor or insulin, on human breast carcinoma cells in the complete absence of estrogens. Moreover, a cytotoxic effect was also observed when the antiestrogens were used at 4 µM concentration or higher. The presence of the estrogen receptor was still necessary for these effects. Therefore, Rochefort 3suggested that these agents be named estrogen receptor targeted drugs, rather than antiestrogens. However, it is a well established clinical fact that TX is capable of inducing regression of tumors that lack the classical receptor for E2.4–6 False negative receptor assay results were proposed as one possibility for this observation. Another possibility is a favorable influence of TX on immune host defence mechanisms. The available evidence supporting this latter possibility is discussed below.
KeywordsMixed Lymphocyte Reaction Human Peripheral Blood Lymphocyte Cytotoxic Reaction Estrogen Receptor Negative Breast Cancer Nonsteroidal Antiestrogen
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- 4.M. Baum, Novaldex Adjuvant Trial Organisation: Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer; analysis at six years, Lancet 1:836(1985).Google Scholar
- 7.E. Baral, H. Blomgren, S. Rotstein and L. Virving, Antiestrogen effects on human blood lymphocyte subpopulations in vitro, J. Clin. Lab. Immunol. 1985; 17:33(1985).Google Scholar
- 14.E. Baral, S. Kwok and I. Berczi, The influence of estradiol and tamoxifen on the mixed lymphocyte reaction in rats, Endocrinology 146:2776(1991).Google Scholar
- 23.W. Troll and J.S. Lim, Tamoxifen suppresses tumor promoter-induced hydrogen peroxide in human neutrophils, Proc. Am. Assn. Cancer Res. 32:149(1991). (Abstract #891)Google Scholar