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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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Summary

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 × 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.

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Authors and Affiliations

  1. Breast Cancer Laboratories, Tenovus Cancer Centre, University of Wales College of Medicine, Heath Park, CF4 4XX, Cardiff, Wales, UK

    Richard A. McClelland, David L. Manning, Julia M. W. Gee & Robert I. Nicholson

  2. Christie Hospital NHS Trust, Manchester, UK

    Elizabeth Anderson, Robert Clarke & Anthony Howell

  3. Royal Marsden Hospital, London, UK

    Mitchell Dowsett

  4. City Hospital, Nottingham, UK

    John F. R. Robertson & Roger W. Blamey

  5. Zeneca Pharmaceuticals, Macclesfield, UK

    Alan E. Wakeling

Authors
  1. Richard A. McClelland
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  2. David L. Manning
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  3. Julia M. W. Gee
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  4. Elizabeth Anderson
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  5. Robert Clarke
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  6. Anthony Howell
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  7. Mitchell Dowsett
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  8. John F. R. Robertson
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  11. Robert I. Nicholson
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McClelland, R.A., Manning, D.L., Gee, J.M.W. et al. Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes. Breast Cancer Res Tr 41, 31–41 (1996). https://doi.org/10.1007/BF01807034

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  • DOI: https://doi.org/10.1007/BF01807034

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