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Series GSE26544 Query DataSets for GSE26544
Status Public on Jul 01, 2011
Title Differentially expressed genes in window trials are influenced by the wound healing process: lessons learned from a pilot study with Anastrozole
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Introduction: Peri-operative window trials, using molecular biomarkers as surrogate endpoints for treatment response, offer investigators a uniqueopportunity to obtain intact tumor samples at 2 different time-points and thus evaluate potential biomarkers over a short period of time. Here we report results of a pilot trial designed to determine if treatment-mediated changes in gene expression can be detected after a 10-day exposure to anastrozole in estrogen receptor (ER)-positive breast cancer compared to untreated controls.
Methods: Paired tumor samples (biopsy and surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer. Patients were assigned anastrozole (1mg/dy) for 10 days immediately prior to surgery (13 cases) or no treatment (13 controls). 502 cancer-related genes were examined by the DASL FFPE-based cDNA array (moderated t-test, p ≤ .005). Surrogate biomarkers reflecting changes in gene expression were examined by immunohistochemistry (IHC) (Wilcoxon rank-based test, p < .05).
Results: Sufficient RNA was available from 19 paired samples (8 controls, 11 cases). There was no difference in age, tumor size, grade, or baseline biomarker expression between groups. Within each group, 18 genes, reflecting roles in proliferation, angiogenesis, and apoptosis showed differential expression over time from biopsy to surgery (p < 0.005). Dysregulation of estrogen-related genes was present only in the treated group. Comparison between groups identified 5 genes that were significantly dysregulated between controls and treated cases (BAG1/ING1/ERBB4/IFNGR1/TFDP1). Reduction in Ki-67 index was observed in 7 (54%) treated cases in 1 (7.7%) control patient.
Conclusions: Short-term (10-day) exposure to anastrozole resulted in significant dysregulation of 18 out of 502 cancer-related genes, and Ki-67 was reduced in 54% of cases. However, the local effects of wound healing may represent a confounding factor in the interpretation of peri-operative window trials as exposed by the changes in gene expression and the increased Ki-67 index in the control group.
 
Overall design Prospective, paired tumor samples (biopsy and surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer. Patients were assigned anastrozole (1mg/dy) for 10 days immediately prior to surgery (13 cases) or no treatment (13 controls). 502 cancer-related genes were examined by the DASL FFPE-based cDNA array. Sufficient RNA for gene expression analysis was obtained from 19/26 (73%) FFPE paired (biopsy and surgery) samples (8 controls, 11 anastrozole-treated patients
 
Contributor(s) King TA, Morrogh M, Andrade VP, Patil AJ, Qin L, Mo Q, Sakr R, Olshen AB, Arroyo C, Brogi E, Morrow M
Citation(s) 21777924
Submission date Jan 11, 2011
Last update date Mar 23, 2012
Contact name Victor Piana Andrade
E-mail(s) andradev@mskcc.org
Phone 646-8883202
Fax 646-8883200
Organization name Memorial Sloan-Kettering Cancer Center
Department Breast Surgery
Lab Tari King
Street address 408E 69th Street z427E
City New York
State/province NY
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL11417 Illumina DASL microarray (Cancer Panel TM v1)
Samples (38)
GSM652674 Invasivebreastca_corebiopsy_notreatment_c10
GSM652675 Invasivebreastca_corebiopsy_notreatment_c13-1
GSM652676 Invasivebreastca_corebiopsy_notreatment_cx2-2
Relations
BioProject PRJNA136623

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