NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE29338 Query DataSets for GSE29338
Status Public on Jul 22, 2011
Title Benign Breast Cores from Healthy Women Treated with Tamoxifen or Placebo
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side-effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for Phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for three months. Blood and breast tissue samples were collected at baseline and post-treatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood, DNA methylation and cytology in random periareolar fine needle aspirates, and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and RT-PCR) in the tissue core samples. Tamoxifen downregulated ets-oncogene family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1 or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen also modulated expression of RAB GTPases, and several genes involved in epithelial-stromal interaction, and reduced tumor suppressor gene methylation. Three months of tamoxifen did not affect breast tissue composition, cytological atypia, preneoplasia or apoptosis. Tamoxifen may durably reduce breast cancer risk through downregulation of ETV4 and ETV5 which could deplete mammary progenitor populations. This pathway has the potential to provide novel targets and early response biomarkers for phase II prevention trials.
 
Overall design Randomized prospective double blinded placebo-controlled trial of tamoxifen (20 mg daily) versus placeo in women at increased risk for breast cancer. Gene expression was assessed in whole breast tissue cores obtained at baseline and after three months of treatment for 35 women. Core biopsies were obtained in the late luteal phase (day 28 +/- 2) for premenopausal women (N = 19). Breast lobules from the baseline and post-treatment cores were microdissected for 5 tamoxifen subjects.
 
Contributor(s) Euhus DM
Citation(s) 21778330
Submission date May 17, 2011
Last update date Feb 18, 2014
Contact name David Euhus
E-mail(s) david.euhus@utsouthwestern.edu
Phone 214-648-6467
Fax 214-648-7965
Organization name UT Southwestern Medical Center
Department Surgery
Street address 5323 Harrry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390-9155
Country USA
 
Platforms (1)
GPL13376 Illumina HumanWG-6 v2.0 expression beadchip
Samples (80)
GSM724745 Benign Breast Core_030_Baseline_Placebo
GSM724746 Benign Breast Core_030_Post-treatment_Placebo
GSM724747 Benign Breast Core_031_Baseline_Tamoxifen
Relations
BioProject PRJNA140143

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE29338_RAW.tar 12.0 Mb (http)(custom) TAR
GSE29338_non-normalized.txt.gz 25.4 Mb (ftp)(http) TXT
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap