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Background: Tamoxifen (TAM) is well established in the adjuvant therapy of breast cancer. However, the timing of TAM therapy, concurrent or after radiotherapy, is controversial., Method: Literature is reviewed with respect to experimental and clinical data on interaction of TAM and radiation on tumor control and radiation side effects., Results: In vitro data support the concept of antagonistic effects of concurrent TAM and radiation on tumor cells, but in animal models a synergistic effect was seen. Considering the modulation of TAM effects by estrogen and growth factor receptors, two-dimensional systems may not be suitable for studying the interaction of TAM and radiation. From a clinical perspective, a tumor-protective effect of TAM therapy concurrent with radiation was not evident. However, prospective studies addressing this question adequately are not available at the time., Conclusion: Although some studies indicate an enhancement of lung and subcutaneous fibrosis after TAM therapy, the side effects are mild and at this point do not seem to warrant withholding TAM.

Background: Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration., Patients and Methods: We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other., Results: Because of its reversibility and patient's compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options., Conclusion: Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45.

In our laboratory the influence of tamoxifen, medroxyprogesterone acetate (MPA) and hydroxyflutamid with and without interferon alpha (IFN) was tested on the proliferative capacity of two breast and one ovarian cancer cell line and three ovarian cancer tissues in the colony assay described by Hamburger and Salmon. The following results were seen: 1. Testing the four drugs alone in 6 different cell cultures, in vitro growth inhibition of more than 30% was seen 3 respectively 4 times. Growth inhibition of more than 50% could be shown only in particular cases. The higher dose of an active substance led up to three times more in comparison to the set growth restraint than the smaller dose. A reaction depending on the concentration was seen. 2. The combination of IFN and tamoxifen could not really increase the antiproliferative capacity of each substance alone. Nevertheless we were able to show a significant augmentation of the cell-growth inhibiting effect of MPA or hydroxyflutamid when it was given together with IFN: the increased antitumor activity was evident if cells were tested which showed progesterone-(PR) or androgenereceptors (AR). The results indicate that positive interactions of IFN and MPA or IFN and hydroxyflutamid are possible. Although an augmentation of the activity of tamoxyfen by IFN was not found it should be stressed that the schedule of treatment seems to be clearly critical.

Murine neuroblastoma (C-1300 NMB) and malignant melanoma (B16) cells were radiated in presence of radiopharmaceutics. Sensibilization was carried out with BSO and protection with TMX. Changes in fluidity of the plasma membrane, in cellular GSH contents and cell cycle were observed. After radiation fluidity of the plasma membrane is increased, whereas intracellular GSH decreased. These changes were intensified by BSO and reduced by TMX. Fluidity of the plasma membrane correlates with intracellular GSH and also with cell cycle. It is suggested that changes in plasma membrane fluidity can be used as an additional parameter for the determination of sensitivity towards radiation.

In 48 postmenopausal breast cancer patients receiving an adjuvant therapy with 30 mg tamoxifen for 22 months on an average the effect of hormonal therapy on different immunologic parameters was examined and compared with an age-matched control group of breast cancer patients without hormonal therapy. Before beginning and after the end of tamoxifen treatment the following examinations were performed: Leucocyte Migrations-Inhibition-Test (LMI-Test) against autologous and homologous tumor and recall antigens, determination of the serum levels of tumor necrosis factor alpha, interleukin 2 and interferon alpha, as well as a determination of lymphocyte subsets (total T-, T-helper-, T-Suppressor- and natural killer cells) in the peripheral blood. Compared to the control group under a tamoxifen therapy the percentage of patients with a migration inhibition in the LMI-test increased, whereas the percentage of patients with an enhancement decreased. There were no changes concerning the LMI-reactivity against recall antigens as well as concerning the serum levels of the different cytokine and the differentiation of T-cell subsets compared to the control group. But we found an increase of natural killer cells. It can be discussed if the clinical effect of a tamoxifen treatment is possibly due to its immunological effect on the nk cell activity.

24 male and 24 female syrian hamsters were treated with antiestrogen Tamoxifen for 21 days (dosage 5, 50, 200 and 800 microgram/d, respectively). For control, 6 male and 6 female animals remained untreated. After having finished this treatment, we performed double-labelling autoradiography with 3H- and 14C-thymidine on all animals, under in vivo-conditions. The number of single labelled 3H-cells has been related to cell proliferation. The quotient " double labelled cells/single 3H-labelled cells " served as a measure for the duration of the S-phase. In addition, we measured the sebaceous gland volume. No essential influence on the parameters could be found. Therefore, we have to assume that the antiestrogen Tamoxifen does not have an essential effect on cell kinetics in the sebaceous gland.

Methods and evaluation of the human tumor stem cell assay (HTSCA) are described. Advantages and disadvantages of the test system are elaborated. The in vitro/in vivo correlation in the drug screening of human ovarian carcinomas shows that the prediction of sensitivity to a cytotoxic agent is only possible in 64%. Prediction of drug resistance, however, seems to be possible in 95%. The number of patients that profit from the HTSCA seems to be only less than 10%. Our investigations describe the influence of various hormones and antiestrogens on the colony formation of human ovarian carcinoma cells. Tamoxifen and his major metabolite 4-hydroxy-tamoxifen were the most active agents. Both compounds inhibit the colony survival (70% at pharmacological concentrations) of 60% of the screened ovarian carcinomas. A significant correlation to the quantitative level of estrogen or progesterone receptors could not be proved. Colony formation of ovarian carcinoma cells was compared in the HTSCA as described by Hamburger and Salmon and in a methylcellulose-monolayer system. Our results show that the colony formation corresponds to the results of the original HTSCA: Cloning ovarian carcinoma cells in the methylcellulose-monolayer, however, seems to be technically easier and faster.

The association of steroids with their cytosol receptors is the first stage in the mechanism of action of steroid hormones. Translocation of the steroid-receptor complex to the nucleus results in the binding of the hormone-receptor complex to chromatin. Subsequently, this process alters gene expression. Oestrogens augment gene expression, leading to cell proliferation and stimulation of protein synthesis. Progesterone may blunt gene expression and antioestrogens act similarly, e.g. tamoxifen inhibits both DNA and protein synthesis. Determination of steroid receptors is a routine diagnostic tool for the management of patients with breast and endometrial cancer.