STEROID-HORMONE RECEPTORS AND ANTINEOPLASTIC CHEMOTHERAPY IN HUMAN BREAST-CANCER

Several clinical and experimental investigations suggest that the acti on of antineoplastic chemotherapy in premenopausal women influences th e menopause. Such hormonal reactions are mediated via specific steroid hormone receptors. Therefore, connections between hormone receptors a nd antineoplastic chemotherapy can be assumed making possible to predi ct success of chemotherapy on the basis of receptor status. Neverthele ss, clinical experiences and animal and cell culture experiments yield ed controversial results. This was related to the predictive value of receptor status as well as to the benefits of combined hormone and che motherapy treatments in concurrent or sequential form. It is undeniabl e that a displacing of steroidal ligand from its receptors by the usua l antineoplastic drugs does not occur. Furthermore, the receptor level s remain unchanged after a treatment with antineoplastic drugs. Thus, the mechanism of action of chemotherapeutic drugs is not related direc tly to the presence or absence of steroid hormone receptors. Despite t his fact the receptor status in chemotherapeutic regimes seems to be h elpful to define low or high risk patients. Influences on the ER de-no vo-synthesis, actions related to parameters representing reduced tumor growth rates, down-regulation of the receptor gene expression or via receptor mediated hormonal actions to other genes, like the apoptosis- related gene bcl-2, are thought to be possible mechanisms of action of antineoplastic drugs on steroid hormone receptors. Future investigati ons should monitor the ratios between exon lacking receptor variants a nd the wild-type receptor during chemotherapy or the control of a liga nd uptake during chemotherapy by means of the positron emission tomogr aphy.