High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: A renewed role for adrenalectomy

Katherine T. Morris, SuEllen Toth-Fejel, Joshua Schmidt, William S. Fletcher, Rodney Pommier

    Research output: Contribution to journalArticle

    51 Citations (Scopus)

    Abstract

    Bachground. Stage IV hormone-sensitive breast cancer is often treated with aromatase inhibitors (anastrozole, letrozole, exemestane), which block the conversion of dehydroepiandrosterone (DHEA) to estrone and estradiol. This is intended to obviate the need for steroid replacement and antiquate adrenalectomy. Methods. Patients who underwent oophorectomy and were being treated with new aromatase inhibitor therapy received serial measurements of serum estrone, estradiol and DHEA-sulfate (DHEA-S). Steroid values during responsive and progressive phases of disease were compared. In vitro, human breast cancer cell lines T-47D (estrogen-receptor and progesterone-receptor positive and HCC 1937 (estrogen-receptor and progesterone-receptor negative) were treated with DHEA-S. Proliferation rates were measured by colorimetric assay. Results. Disease in 12 of the 19 patients progressed. DHEA-S was less than 89 μg/dL in patients during the responsive phase and more than or equal to 89 μg/dL during disease progression, with 1 exception (P <.0005). Estrone and estradiol remained suppressed. After disease progression, the condition of 9 patients stabilized with aminoglutethimide therapy (n = 8) or adrenalectomy (n = 1), and their DHEA-S levels were reduced to less than 89 μg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells. Conclusions. DHEA-S levels more than or equal to 89 μg/dL predicted disease progression in states of low estrogen. Tissue culture results supported the role of DHEA-S as an estrogenic agent. Oophorectomies with either aminoglutethimide therapy or adrenalectomy were effective remedies for breast cancer progression due to high DHEA-S.

    Original languageEnglish (US)
    Pages (from-to)947-953
    Number of pages7
    JournalSurgery
    Volume130
    Issue number6
    DOIs
    StatePublished - 2001

    Fingerprint

    Dehydroepiandrosterone Sulfate
    Aromatase Inhibitors
    Dehydroepiandrosterone
    Adrenalectomy
    Breast Neoplasms
    Growth
    Estrone
    Aminoglutethimide
    Disease Progression
    exemestane
    Therapeutics
    letrozole
    Ovariectomy
    Progesterone Receptors
    Estrogen Receptors
    Estradiol
    Estrogens
    Steroids
    Cell Proliferation
    Hormones

    ASJC Scopus subject areas

    • Surgery

    Cite this

    High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture : A renewed role for adrenalectomy. / Morris, Katherine T.; Toth-Fejel, SuEllen; Schmidt, Joshua; Fletcher, William S.; Pommier, Rodney.

    In: Surgery, Vol. 130, No. 6, 2001, p. 947-953.

    Research output: Contribution to journalArticle

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    abstract = "Bachground. Stage IV hormone-sensitive breast cancer is often treated with aromatase inhibitors (anastrozole, letrozole, exemestane), which block the conversion of dehydroepiandrosterone (DHEA) to estrone and estradiol. This is intended to obviate the need for steroid replacement and antiquate adrenalectomy. Methods. Patients who underwent oophorectomy and were being treated with new aromatase inhibitor therapy received serial measurements of serum estrone, estradiol and DHEA-sulfate (DHEA-S). Steroid values during responsive and progressive phases of disease were compared. In vitro, human breast cancer cell lines T-47D (estrogen-receptor and progesterone-receptor positive and HCC 1937 (estrogen-receptor and progesterone-receptor negative) were treated with DHEA-S. Proliferation rates were measured by colorimetric assay. Results. Disease in 12 of the 19 patients progressed. DHEA-S was less than 89 μg/dL in patients during the responsive phase and more than or equal to 89 μg/dL during disease progression, with 1 exception (P <.0005). Estrone and estradiol remained suppressed. After disease progression, the condition of 9 patients stabilized with aminoglutethimide therapy (n = 8) or adrenalectomy (n = 1), and their DHEA-S levels were reduced to less than 89 μg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells. Conclusions. DHEA-S levels more than or equal to 89 μg/dL predicted disease progression in states of low estrogen. Tissue culture results supported the role of DHEA-S as an estrogenic agent. Oophorectomies with either aminoglutethimide therapy or adrenalectomy were effective remedies for breast cancer progression due to high DHEA-S.",
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