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Estrogen Receptor-alpha Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer
Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands.
Lund Univ, Malmo Univ Hosp, Ctr Mol Pathol, Malmo, Sweden.
Netherlands Canc Inst, Dept Bioinformat and Stat, Amsterdam, Netherlands.
Netherlands Canc Inst, Dept Tumor Biol, Amsterdam, Netherlands.
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2009 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, Vol. 101, no 24, 1725-1729 p.Article in journal (Refereed) Published
Abstract [en]

Although estrogen receptor-alpha (ER alpha) is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ER alpha-positive breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ER alpha at serine-118 (ER alpha S118-P) is required for tamoxifen-mediated inhibition of ER alpha-induced gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ER alpha S118-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. ER alpha S118-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 ER alpha S118-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.

Place, publisher, year, edition, pages
2009. Vol. 101, no 24, 1725-1729 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-52864DOI: 10.1093/jnci/djp412OAI: diva2:285791
Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2010-01-13

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Stål, Olle
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Oncology Faculty of Health SciencesDepartment of Oncology UHL
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