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Dehydroepiandrosterone Sulfate Causes Proliferation of Estrogen ReceptorPositive Breast Cancer Cells Despite Treatment With Fulvestrant
Kristine E. Calhoun, MD;
Rodney F. Pommier, MD;
Patrick Muller, BS;
William S. Fletcher, MD;
SuEllen Toth-Fejel, PhD
Arch Surg. 2003;138:879-883.
Hypothesis Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182 780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells.
Design Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S.
Setting Surgical oncology research laboratory.
Interventions The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 µg/dL (22.8 µmol/L) of DHEA-S.
Main Outcome Measures Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change.
Results The ER-positive and progesterone receptorpositive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptornegative cells demonstrated growth inhibition.
Conclusions The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
From the Division of Surgical Oncology, Department of General Surgery, Oregon Health and Sciences University, Portland.
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