Background: Dehydroepiandosterone sulfate (DHEAS) causes breast-cancer proliferation, even during tamoxifen or fulvestrant blockade. The purpose of this study was to determine possible mechanisms for this treatment failure.
Methods: T-47D cells (estrogen receptor [ER] and progesterone receptor [PR] positive) were treated with fulvestrant (10 micromol/L), tamoxifen (10 mmol/L or 0.0001 nmol/L), or vehicle and stimulated with DHEAS. Gene expression of ER, PR, insulin-like growth factor (IGF)-1 and -2, and insulin-like growth-factor binding protein (IGFBP)-1 through -4 was determined.
Results: ER and PR gene expression decreased by 1.3- and 4-fold with fulvestrant and DHEAS. ER expression decreased by 2.7-fold with 0.0001 nmol/L tamoxifen and DHEAS. ER and PR expression were unchanged by 10 nmol/L tamoxifen. IGF-1 and IGF-2 were not expressed. IGFBP-2 and -4 expression decreased by 1.9- and 1.6-fold after DHEAS stimulus, although this was not statistically significant.
Conclusions: DHEAS exposure, even in the presence of tamoxifen and fulvestrant, induces changes in ER and PR gene expression that may be partially responsible for breast cancer progression.