Τόμος 4 (1986) – Τεύχος 4 – Άρθρο 4 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 4 (1986) – Issue 4 – Article 4 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

M. N. ALEXIS

4: 199-213 (1986)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

4: 199-213 (1986)

It is well known that tumors that initially regress after hormonal therapy with non-steroidal antioestrogens (e.g. tamoxi­fen), they tend to recur as a non-responding type. The problem is discussed on the basis of data showing that the mitogenic effect of oe­strogens can be both direct i.e. mediated by oestrogen receptor (ER) and indirect i.e. media­ted by oestrogen-induced growth factors (oe­stromedins: EM). Since tamoxifen is inhibiting cell proliferation, more likely by affecting nu­clear oestrogen receptor turnover at relatively high concentration, but is an agonist by its ability to induce oestrogen regulated proteins and oestromedins, its effect on differentiated oestrogen target-tissues can vary, as it is de­pendent on the mechanism of action of oestro­gens in the particular tissue. In breast tumors, known to comprise both ER positive as well as ER negative cells possibly regulated by EM, its effect is not expected to be always beneficial. Furthermore, since it is inhibiting proliferation of ER positive tumor cells, when combined with cytotoxic chemotherapy it is likely to counteract its effectiveness. Hence, by taking into account that tamoxifen blocks cycling cells at a parti­cular point at the G₁ phase of the cycle, oe­strogen relief of the block followed by chemo­therapy can be proposed.

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