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What do we know and what don't we know about tamoxifen in the human uterus

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Abstract

Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expanded. Tamoxifen is now used for the treatment of metastatic breast cancer and for long-term and often indefinite administration as an adjuvant therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen therapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this controversial issue can be summarized as follows:

  1. a)

    Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen levels.

  2. b)

    Tamoxifen treatment is probably associated with an increased incidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40mg/d).

  3. d)

    It is not known whether tamoxifen causes or allows the identification of occult endometrial carcinoma.

  4. e)

    At the present time there is evidence for a tumor promoting effect of tamoxifen on endometrial cancer at a dose of 20 mg per day.

  5. f)

    Replacement of tamoxifen by ‘pure’ antiestrogens or coadministration of progestins with tamoxifen do not appear to offer benefit unless clinical trials demonstrate a reduced incidence of endometrial problems.

  6. g)

    Patientsmust be evaluated for pre-exsisting endometrical carcinoma before starting tamoxifen therapy.

  7. f)

    Close followup of long-term tamoxifen patients with endometrial biopsies is recommended with individuals who experience symptoms.

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Abbreviations

DMBA:

7,12-dimethylbenzanthracene

FSH:

follicle stimulating hormone

LH:

luteinizing hormone

GH:

growth hormone

IGF-1:

insulin-like growth factor 1

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  1. Department of Pathology and Laboratory Medicine, University of Wisconsin Medical Sciences Center, 53706, Madison, WI, USA

    Andreas Friedl

  2. Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, 53792, Madison, WI, USA

    V. Craig Jordan

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Friedl, A., Jordan, V.C. What do we know and what don't we know about tamoxifen in the human uterus. Breast Cancer Res Tr 31, 27–39 (1994). https://doi.org/10.1007/BF00689674

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