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    Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes.

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    Authors
    McClelland, R A
    Manning, D L
    Gee, J M
    Anderson, Elizabeth
    Clarke, Robert B
    Howell, Anthony
    Dowsett, M
    Robertson, J F
    Blamey, R W
    Wakeling, A E
    Nicholson, R I
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    Affiliation
    Tenovus Cancer Research Centre, Cardiff, UK.
    Issue Date
    1996
    
    Metadata
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    Abstract
    Effects of the pure antiestrogen ICI182780 and tamoxifen on ER-protein, ER-mRNA, and estrogen-regulated mRNA expression were analysed using matched pretreatment core-cut biopsies and post-treatment mastectomy samples from 43 ER positive human breast cancers. Sixteen controls received either no preoperative treatment (n = 9) (7 days) or placebo (n = 7) (median 21 days) prior to primary surgery. Nineteen patients received ICI182780 6 mg/day (n = 10) or 18 mg/day (n = 9) for 7 days. Eight patients were given preoperative tamoxifen (4 x 40 mg-day 1, 20 mg/day thereafter, median 21 days). ER-protein expression was assessed on pre and post treatment samples by immunocytochemistry. ER, pS2, pLIV1, and actin-mRNA expression was determined by northern analysis on post-treatment samples only. ER-mRNA levels were similar to controls following ICI182780 or tamoxifen treatment. However ER-protein levels were significantly suppressed by ICI182780, particularly at the higher dosage (p = 0.0013). Tamoxifen had no significant effect on ER-protein levels. The ER-mRNA and ER-protein contents of control tumors were linearly related (Spearman r = 0.719, p = 0.006). A similar relationship between pretreatment protein and post ICI182780 treatment mRNA levels was observed (r = 0.652, p = 0.005). However, comparison of post ICI182780 treatment protein and mRNA results shows a loss of linearity through a reduction in protein without concurrent loss of mRNA (r = 0.28, p = 0.257). pS2 mRNA hybridization was lower in ICI182780 treated samples than controls (Mann-Whitney p = 0.035) but was unaffected by tamoxifen. pLIV1 mRNA hybridization was uninfluenced by either treatment. Short term exposure of breast tumors to ICI182780 appears to produce a greater inhibition of estrogen-induced transcriptional events than tamoxifen. These effects appear to occur without a concurrent reduction in ER mRNA levels.
    Citation
    Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes. 1996, 41 (1):31-41 Breast Cancer Res. Treat.
    Journal
    Breast Cancer Research and Treatment
    URI
    http://hdl.handle.net/10541/95702
    DOI
    10.1007/BF01807034
    PubMed ID
    8932874
    Type
    Article
    Language
    en
    ISSN
    0167-6806
    ae974a485f413a2113503eed53cd6c53
    10.1007/BF01807034
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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