The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression

Kristine Calhoun, Rodney Pommier, Julie Cheek, William Fletcher, SuEllen Toth-Fejel

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Background: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. Methods: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 μM anastrozole, with or without tamoxifen, and stimulated with 22.8 μM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. Results: Clinically, development of metastatic disease correlated only with ≥90 μg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. Conclusions: DHEA-S ≥90 μg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.

    Original languageEnglish (US)
    Pages (from-to)411-415
    Number of pages5
    JournalAmerican Journal of Surgery
    Volume185
    Issue number5
    DOIs
    StatePublished - May 1 2003

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    Dehydroepiandrosterone Sulfate
    Tamoxifen
    Breast Neoplasms
    Dehydroepiandrosterone
    Growth
    Gonadal Steroid Hormones
    Disease Progression
    Recurrence
    Serum

    Keywords

    • Breast cancer
    • DHEA-S
    • Tamoxifen

    ASJC Scopus subject areas

    • Surgery

    Cite this

    The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression. / Calhoun, Kristine; Pommier, Rodney; Cheek, Julie; Fletcher, William; Toth-Fejel, SuEllen.

    In: American Journal of Surgery, Vol. 185, No. 5, 01.05.2003, p. 411-415.

    Research output: Contribution to journalArticle

    Calhoun, Kristine ; Pommier, Rodney ; Cheek, Julie ; Fletcher, William ; Toth-Fejel, SuEllen. / The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression. In: American Journal of Surgery. 2003 ; Vol. 185, No. 5. pp. 411-415.
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    abstract = "Background: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. Methods: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 μM anastrozole, with or without tamoxifen, and stimulated with 22.8 μM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. Results: Clinically, development of metastatic disease correlated only with ≥90 μg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35{\%} increased growth. Addition of 0.01 nM tamoxifen demonstrated -7{\%} inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25{\%}. Conclusions: DHEA-S ≥90 μg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.",
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