[The clinical value of hormone receptors in the treatment of breast neoplasms].
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Biomedical subjects
Publications and source records attributed to G Trams.
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Steroidal alkylating agents are supposed to bind to steroid hormone receptors in target tissues. By this interaction the steroid portion might act as a carrier for the alkylating group. Three steroidal agents (phenesterin, estradiol mustard, dehydroepiandrosterone mustard) were tested for their capacity to combine with estrogen and androgen receptors in normal and malignant target tissues. For measuring steroid receptor complexes ager gel electrophoresis was used. All three compounds (added at a 10(3)-fold excess) revealed in vitro no competition to receptor sites (estrogen and androgen binding). After preincubation of intact tissue estrogen mustard was effective in inhibiting the binding of 3H-estradiol and dehydroepiandrosterone mustard reduced the uptake of 3H-5alpha-DHT. This may be due to liberating of estradiol and dehydroepiandrosterone, respectively, from the intact molecule. From these data it is unlikely that the cytostatic steroidal agents are more effective than other alkylating drugs.
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After injection of radioactively labelled cortisol, the distribution of the radioactivity in the subcellular fractions of the rat uterus (nuclei, mitochondria, microsomes and 105 000 X g supernatant) was studied. In all fractions, radioactivity was observed and maxima were found 10, 20 and 50 min. after injection of the labelled hormone. Radioactivity was measured in all subcellular fractions even 180 min. after application of labelled cortisol. Additionally, radiolabelled progesterone and unlabelled cortisol in the ratio 1:1 or 1:2 (moles:moles) were injected into the animals. Studying the uptake of labelled progesterone in the subcellular fractions of the uterine tissue, revealed that no competition of unlabelled cortisol could be observed 10, 20 and 50 min. after application of the hormone mixture, compared with the control experiments. The results of this study give evidence that the progesterone uptake into rat uterus is specific and cannot be influenced by unlabelled cortisol.
A study of the subcellular distribution of radioactivity in rat uterus after injection of labelled corticosterone showed that the radioactivity was observed in all fractions from 5 min. to 120 min. A maximum uptake was observed 10 min. after application of the labelled steroid. Competitive uptake of radioactive progesterone and unlabelled corticosterone was assayed 10 min. after injection of the hormone mixture. The ratio between radioactive progesterone and unlabelled corticosterone was 1:1 and 1:2 (moles:moles), respectively. Compared with control experiments with rats which had received radioactive progesterone alone, the results gave evidence that progesterone found in all subcellular fractions and in the total homogenate was not depressed by unlabelled corticosterone. However, unlabelled progesterone reduced the tritiated progesterone in uterine tissue. This observation demonstrates that the uptake of progesterone by rat uterus is specific.
Estrogen and dihydrotestosterone receptors were detected by agar gel electrophoresis in 224 human mammary tumor biopsies. Approximately half of the tumor specimens revealed measurable amounts of estradiol receptors, whereas only 20% contained dihydrotestosterone receptors. The average concentration of spare estrogetmenopausal than in the premenopausal group, but this was not found to be the case for androgen receptors. The findings presented are discussed with regard to the clinical relevance of multiple assays for various types of receptors in a single tumor.
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Human breast cancer was studied by in vitro techniques on tissue slices and extracts for a specific binding of estradiol and dihydrotestosterone. Estradiol receptors were found in 50 percent of patients in the premenopausal group and in 47 percent of patients in the postmenopausal group. The incidence of receptors in patients with metastatic disease was 32.5 percent. In 18 of 35 patients who were positive for receptor sites a remission was observed after a variety of endocrine treatment regimens. In contrast only 3 patients out of 43 with a negative binding pattern responded to treatment with nafoxidine for a very short time. The best correlation was found in the ovariectomized group. Between the responders and the nonresonders there is no difference in the quantitative receptor content. The same is valid in view of the duration of the remission.
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