Unknown,Multiomics

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12

Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial


ABSTRACT: Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer. In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT. Keywords: Gene expression profiling analysis Formalin fixed paraffin embedded tumor blocks with enough tumor tissue for RNA extraction were available from 108 cases (69 from placebo arm and 39 from tamoxifen arm) of the 264 that experienced invasive breast cancer (175 in placebo arm and 89 in tamoxifen arm) in BCPT before unblindings . Central ER immunohistochemistry identified 84 of them as ER positive (57 from placebo arm and 27 from tamoxifen arm). A novel protocol was developed and used to obtain microarray gene expression profiling from the degraded or fragmented RNA extracted from formalin fixed paraffin blocks.Hybridization intensity data were compiled using Partek Genomic Suite. After quantile normalization, genes with mean intensity below 500 were filtred out, which left 7743 probes with informative data. Data were log2 transformed for statistical analysis.

OTHER RELATED OMICS DATASETS IN: PRJNA112733

PROVIDER: E-GEOD-12665 | ExpressionAtlas | 2015-08-06

REPOSITORIES: ExpressionAtlas

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Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer.

Kim Chungyeul C   Tang Gong G   Pogue-Geile Katherine L KL   Costantino Joseph P JP   Baehner Frederick L FL   Baker Joffre J   Cronin Maureen T MT   Watson Drew D   Shak Steven S   Bohn Olga L OL   Fumagalli Debora D   Taniyama Yusuke Y   Lee Ahwon A   Reilly Megan L ML   Vogel Victor G VG   McCaskill-Stevens Worta W   Ford Leslie G LG   Geyer Charles E CE   Wickerham D Lawrence DL   Wolmark Norman N   Paik Soonmyung S  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20110926 31


<h4>Purpose</h4>Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) -positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used cl  ...[more]

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