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Series GSE179674 Query DataSets for GSE179674
Status Public on Jul 08, 2021
Title Genome wide gene expression profiling of pre and post treatment breast cancer biopsy
Organism Homo sapiens
Experiment type Expression profiling by array
Summary In breast cancer models, combination epigenetic therapy with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor led to reexpression of genes encoding important therapeutic targets, including the estrogen receptor (ER). We conducted a multicenter phase II study of 5-azacitidine and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC).
Purpose: In breast cancer models, combination epigenetic therapy with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor led to re-expression of genes encoding important therapeutic targets including the estrogen receptor (ER). We conducted a multicenter phase II study of 5-azacitidine (AZA) and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC). Patients and Methods: Patients received AZA 40 mg/m2 (days 1-5, 8-10) and entinostat 7 mg (days 3,10) of 28 day cycle. Continuation of epigenetic therapy was offered with addition of endocrine therapy at time of progression (optional continuation, OC phase). Primary endpoint was objective response rate (ORR) in each cohort. We hypothesized that ORR would be >20% against null of 5% using Simon two-stage design. At least 1 response was required in 1st of 13 patients per cohort to continue accrual to 27 per cohort. Type I error 4%, power 90%. Results: There was one partial response among 27 women with hormone-resistant disease (ORR=4%, 95% CI=0-19%), and none in 13 women with TNBC. One additional partial response was observed in the OC phase in the hormone-resistant cohort (n=12). Mandatory tumor samples were obtained pre- and post-treatment (58% paired) with either up- or down-regulation of ER observed in approximately 50% of post-treatment biopsies in the hormone-resistant, but not TNBC cohort. Conclusion: Combination epigenetic therapy was well tolerated but our primary endpoint was not met. OC phase results suggest that some women benefit from epigenetic therapy and/or reintroduction of endocrine therapy beyond progression but further study is needed.
 
Overall design Two-condition experiment, pre and post treatment. Two color array was used as one color by single channel
 
Contributor(s) Connolly RM, Lii H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff  AC, Fetting JH, Brufsky A, Piekarz  R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V
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Submission date Jul 07, 2021
Last update date Jul 09, 2021
Contact name leslie cope
E-mail(s) cope@jhu.edu
Organization name leslie cope
Street address 550 N. Broadway
City Baltimore
State/province MD
ZIP/Postal code 21209
Country USA
 
Platforms (1)
GPL10332 Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Feature Number version)
Samples (46)
GSM5426096 Primary breast tissue #1 Sample 1 Cy3
GSM5426097 Primary breast tissue #1 Sample 1 Cy5
GSM5426098 Primary breast tissue #2 Sample 2 Cy3
Relations
BioProject PRJNA744526

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
GSE179674_RAW.tar 719.3 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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