STEROID-HORMONE RECEPTORS AND HORMONAL THERAPIES IN HUMAN BREAST-CANCER

By reason of therapeutic implications of steroid receptors in breast c ancer most of investigations on estradiol and progesterone receptor ex pression have focused on the predictive and prognostic importance of t hese receptors. The introduction of immunological methods for receptor estimation opened a new understanding of receptor behaviour under inf luence of different therapeutic means; as tamoxifen or medroxyprogeste rone acetate. This rendered ER up-regulation by tamoxifen or possible influence of short term tamoxifen application able to prevent false ne gative results induced by an estradiol mediated down-regulation of the estradiol receptor. Other aspects refer to the existence of receptor variants and an acquired decrease of receptor affinity developed under long term tamoxifen application. Furthermore, receptors seem to be in volved into mechanism of estradiol and tamoxifen action in invasion an d metastasis. In contrast, aromatase inhibitors seem to exert its effe cts more via transcription resulting in ER and PR down regulation than by direct effects on receptors levels. Despite a clear prognostic imp ortance of both receptors in case of therapy with gestagenic derivativ es much more important is maintenance of a high serum level of medroxy progesterone acetate. Altogether, a positive receptor status predicts a better therapeutic response of any endocrine therapy than a receptor negative status. This statement seems to be more related to receptors as basic biological parameters reflecting differentiation and prolife rative activity than its direct inclusion into mechanisms of action of the several therapy modalities.