Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Phosphorylation of oestrogen receptor alpha at serine 305 (ERalphaS305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ERalphaS305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ERalphaS305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ERalphaS305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ERalphaS305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ERalphaS305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ERalphaS305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ERalphaS305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Detaljer

Författare
  • Caroline Wigerup
  • M Kok
  • R Michalides
  • R Fles
  • Rht Koornstra
  • J Wesseling
  • M Hauptmann
  • J Neefjes
  • Jl Peterse
  • O Stål
  • Göran Landberg
  • Sc Linn
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)372-379
TidskriftJournal of Pathology
Volym2008
Utgåva nummerSep 23
StatusPublished - 2009
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Caroline Wigerup, 2009, Department of Laboratory Medicine, Lund University. 121 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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