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Estrogen Receptor-{alpha} Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer.

Kok, Marleen; Wigerup, Caroline LU ; Hauptmann, Michael; Michalides, Rob; Stål, Olle; Linn, Sabine and Landberg, Göran LU (2009) In Journal of the National Cancer Institute 101(24). p.1725-1729
Abstract
Although estrogen receptor-alpha (ERalpha) is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ERalpha-positive breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ERalpha at serine-118 (ERalphaS118-P) is required for tamoxifen-mediated inhibition of ERalpha-induced gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ERalphaS118-P expression by use of Cox proportional hazards regression. Data were from 239 premenopausal patients with breast cancer who participated in a randomized trial of 2 years of adjuvant tamoxifen treatment vs no systemic treatment. ERalphaS118-P... (More)
Although estrogen receptor-alpha (ERalpha) is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ERalpha-positive breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ERalpha at serine-118 (ERalphaS118-P) is required for tamoxifen-mediated inhibition of ERalpha-induced gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ERalphaS118-P expression by use of Cox proportional hazards regression. Data were from 239 premenopausal patients with breast cancer who participated in a randomized trial of 2 years of adjuvant tamoxifen treatment vs no systemic treatment. ERalphaS118-P expression was assessed by immunohistochemistry and categorized by use of the Allred score (low expression = score of 0-6; high expression = score of 7-8). All statistical tests were two-sided. Compared with systemically untreated patients, we found evidence of a benefit from adjuvant tamoxifen among patients whose tumors had high ERalphaS118-P expression (23.7 recurrences per 1000 person-years versus 72.2 recurrences per 1000 person-years, hazard ratio [HR] of recurrence = 0.36, 95% confidence interval [CI] = 0.20 to 0.65) but not among patients whose tumors had low expression (51.0 recurrences per 1000 person-years versus 57.0 recurrences per 1000 person-years, HR of recurrence = 0.87, 95% CI = 0.51 to 1.48. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the National Cancer Institute
volume
101
issue
24
pages
1725 - 1729
publisher
Oxford University Press
external identifiers
  • wos:000272933400011
  • pmid:19940281
  • scopus:72649090647
ISSN
1460-2105
DOI
10.1093/jnci/djp412
language
English
LU publication?
yes
id
c6f5f619-b816-4ad2-8211-737973c5d84b (old id 1511542)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19940281?dopt=Abstract
date added to LUP
2009-12-07 11:29:33
date last changed
2017-11-19 03:57:24
@article{c6f5f619-b816-4ad2-8211-737973c5d84b,
  abstract     = {Although estrogen receptor-alpha (ERalpha) is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ERalpha-positive breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ERalpha at serine-118 (ERalphaS118-P) is required for tamoxifen-mediated inhibition of ERalpha-induced gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ERalphaS118-P expression by use of Cox proportional hazards regression. Data were from 239 premenopausal patients with breast cancer who participated in a randomized trial of 2 years of adjuvant tamoxifen treatment vs no systemic treatment. ERalphaS118-P expression was assessed by immunohistochemistry and categorized by use of the Allred score (low expression = score of 0-6; high expression = score of 7-8). All statistical tests were two-sided. Compared with systemically untreated patients, we found evidence of a benefit from adjuvant tamoxifen among patients whose tumors had high ERalphaS118-P expression (23.7 recurrences per 1000 person-years versus 72.2 recurrences per 1000 person-years, hazard ratio [HR] of recurrence = 0.36, 95% confidence interval [CI] = 0.20 to 0.65) but not among patients whose tumors had low expression (51.0 recurrences per 1000 person-years versus 57.0 recurrences per 1000 person-years, HR of recurrence = 0.87, 95% CI = 0.51 to 1.48.},
  author       = {Kok, Marleen and Wigerup, Caroline and Hauptmann, Michael and Michalides, Rob and Stål, Olle and Linn, Sabine and Landberg, Göran},
  issn         = {1460-2105},
  language     = {eng},
  number       = {24},
  pages        = {1725--1729},
  publisher    = {Oxford University Press},
  series       = {Journal of the National Cancer Institute},
  title        = {Estrogen Receptor-{alpha} Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer.},
  url          = {http://dx.doi.org/10.1093/jnci/djp412},
  volume       = {101},
  year         = {2009},
}