The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy: Implications for Treatment and Protocol Planning

Rodney Pommier, Eugene A. Woltering, Edward J. Keenan, William S. Fletcher

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Fifteen patients whose tumors progressed while they received tamoxifen citrate therapy were studied by serial determinations of serum levels of estrone (E1), estradiol (E2), and dehydroepiandrosterone (DHEA) obtained during progression after withdrawal from tamoxifen therapy and total endocrine ablation or suppression. Discontinuation of tamoxifen therapy resulted in reductions of DHEA, E1, and E2 levels by 44%, 49%, and 42%, respectively. Ablation or suppression reduced sex steroids to minimal levels and produced responses in all patients. Elevations of DHEA, E1, and E2 could be provoked by readministering tamoxifen to hypophysectomized and oophorectomized, but not adrenalectomized, patients, indicating that the adrenal gland is the source of these sex steroids. We conclude that tamoxifen stimulates adrenal production of DHEA, which is aromatized to E2 and E2. Buildup of E1 and E2 overwhelms the competitive binding of tamoxifen to the estrogen receptor, resulting in tumor progression.

    Original languageEnglish (US)
    Pages (from-to)1311-1316
    Number of pages6
    JournalArchives of Surgery
    Volume122
    Issue number11
    DOIs
    StatePublished - 1987

    Fingerprint

    Estrogen Receptor Modulators
    Tamoxifen
    Clinical Protocols
    Dehydroepiandrosterone
    Hormones
    Breast Neoplasms
    Therapeutics
    Steroids
    Competitive Binding
    Estrone
    Adrenal Glands
    Estrogen Receptors
    Estradiol
    Neoplasms
    Serum

    ASJC Scopus subject areas

    • Surgery

    Cite this

    The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy : Implications for Treatment and Protocol Planning. / Pommier, Rodney; Woltering, Eugene A.; Keenan, Edward J.; Fletcher, William S.

    In: Archives of Surgery, Vol. 122, No. 11, 1987, p. 1311-1316.

    Research output: Contribution to journalArticle

    Pommier, Rodney ; Woltering, Eugene A. ; Keenan, Edward J. ; Fletcher, William S. / The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy : Implications for Treatment and Protocol Planning. In: Archives of Surgery. 1987 ; Vol. 122, No. 11. pp. 1311-1316.
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