Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.
OBJECTIVE
Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells.


METHODS
Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S.


METHODS
Surgical oncology research laboratory.


METHODS
The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S.


METHODS
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.
Calhoun
Kristine E
KE
Department of General Surgery, Oregon Health and Sciences University, Portland, OR 97201, USA.
Pommier
Rodney F
RF
Muller
Patrick
P
Fletcher
William S
WS
Toth-Fejel
SuEllen
S
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D066298:In Vitro Techniques; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate