WHAT DO WE KNOW AND WHAT DONT WE KNOW ABOUT TAMOXIFEN IN THE HUMAN UTERUS

Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expan ded. Tamoxifen is now used for the treatment of metastatic breast canc er and for long-term and often indefinite administration as an adjuvan t therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen t herapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this cont roversial issue can be summarized as follows: a) Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen leve ls. b) Tamoxifen treatment is probably associated with an increased in cidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40mg/d). d) It is not known whether tamoxifen causes or allows the identification of occult endometrial c arcinoma. e) At the present time there is evidence for a tumor promoti ng effect of tamoxifen on endometrial cancer at a dose of 20 mg per da y. f) Replacement of tamoxifen by 'pure' antiestrogens or coadministra tion of progestins with tamoxifen do not appear to offer benefit unles s clinical trials demonstrate a reduced incidence of endometrial probl ems. g) Patients must be evaluated for pre-exsisting endometrical carc inoma before starting tamoxifen therapy. f) Close followup of long-ter m tamoxifen patients with endometrial biopsies is recommended with ind ividuals who experience symptoms.