Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant

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 mug/dL (22.8 mumol/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 receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. Conclusions: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.