Estrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer.
AffiliationDepartment of Experimental Therapy, Netherlands Cancer Institute, Amsterdam, The Netherlands.
MetadataShow full item record
AbstractAlthough 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.
CitationEstrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer. 2009, 101 (24):1725-9 J. Natl. Cancer Inst.
JournalJournal of the National Cancer Institute
- Association between Pak1 expression and subcellular localization and tamoxifen resistance in breast cancer patients.
- Authors: Holm C, Rayala S, Jirström K, Stål O, Kumar R, Landberg G
- Issue date: 2006 May 17
- Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance.
- Authors: Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, Elledge RM
- Issue date: 2005 Sep 7
- Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93.
- Authors: International Breast Cancer Study Group, Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD
- Issue date: 2006 Mar 20
- PKA-induced phosphorylation of ERα at serine 305 and high PAK1 levels is associated with sensitivity to tamoxifen in ER-positive breast cancer.
- Authors: Kok M, Zwart W, Holm C, Fles R, Hauptmann M, Van't Veer LJ, Wessels LF, Neefjes J, Stål O, Linn SC, Landberg G, Michalides R
- Issue date: 2011 Jan
- Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor α.
- Authors: Barone I, Brusco L, Gu G, Selever J, Beyer A, Covington KR, Tsimelzon A, Wang T, Hilsenbeck SG, Chamness GC, Andò S, Fuqua SA
- Issue date: 2011 Apr 6