Estrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91622
Title:
Estrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer.
Authors:
Kok, Marleen; Holm-Wigerup, Caroline; Hauptmann, Michael; Michalides, Rob; Stål, Olle; Linn, Sabine; Landberg, Goran
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.
Affiliation:
Department of Experimental Therapy, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Citation:
Estrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer. 2009, 101 (24):1725-9 J. Natl. Cancer Inst.
Journal:
Journal of the National Cancer Institute
Issue Date:
16-Dec-2009
URI:
http://hdl.handle.net/10541/91622
DOI:
10.1093/jnci/djp412
PubMed ID:
19940281
Type:
Article
Language:
en
ISSN:
1460-2105
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKok, Marleenen
dc.contributor.authorHolm-Wigerup, Carolineen
dc.contributor.authorHauptmann, Michaelen
dc.contributor.authorMichalides, Roben
dc.contributor.authorStål, Olleen
dc.contributor.authorLinn, Sabineen
dc.contributor.authorLandberg, Goranen
dc.date.accessioned2010-02-09T14:45:20Z-
dc.date.available2010-02-09T14:45:20Z-
dc.date.issued2009-12-16-
dc.identifier.citationEstrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer. 2009, 101 (24):1725-9 J. Natl. Cancer Inst.en
dc.identifier.issn1460-2105-
dc.identifier.pmid19940281-
dc.identifier.doi10.1093/jnci/djp412-
dc.identifier.urihttp://hdl.handle.net/10541/91622-
dc.description.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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectOestrogen Receptor alphaen
dc.subject.meshAntineoplastic Agents, Hormonal-
dc.subject.meshBreast Neoplasms-
dc.subject.meshDisease-Free Survival-
dc.subject.meshEstrogen Receptor alpha-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLymphatic Metastasis-
dc.subject.meshMultivariate Analysis-
dc.subject.meshOdds Ratio-
dc.subject.meshPhosphorylation-
dc.subject.meshPremenopause-
dc.subject.meshProportional Hazards Models-
dc.subject.meshSerine-
dc.subject.meshTamoxifen-
dc.titleEstrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Therapy, Netherlands Cancer Institute, Amsterdam, The Netherlands.en
dc.identifier.journalJournal of the National Cancer Instituteen

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