Understanding the biologic mechanisms responsible for breast-cancer progression during tamoxifen or fulvestrant treatment.
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.
Division of Surgical Oncology, Department of General Surgery, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., I.223A, Portland, OR 97201-3098, USA.
Chelsea
C
Hardin
Rodney
R
Pommier
Brett
B
Lefleur
Terisa
T
Jackson
Suellen
S
Toth-Fejel
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D018450:Disease Progression; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D013629:Tamoxifen / Q000627:therapeutic use*; D017211:Treatment Failure; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate