Estrogen Receptor-α Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer
Autor: | Michael Hauptmann, Rob Michalides, Caroline Holm-Wigerup, Olle Stål, Sabine C. Linn, Göran Landberg, Marleen Kok |
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Rok vydání: | 2009 |
Předmět: |
Oncology
Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal Breast Neoplasms Disease-Free Survival Breast cancer Internal medicine Odds Ratio Serine Humans Medicine Phosphorylation Proportional Hazards Models business.industry Hazard ratio Estrogen Receptor alpha Cancer Antiestrogen medicine.disease Immunohistochemistry Tamoxifen Endocrinology Premenopause Selective estrogen receptor modulator Lymphatic Metastasis Multivariate Analysis Female Breast disease business Estrogen receptor alpha medicine.drug |
Zdroj: | JNCI: Journal of the National Cancer Institute. 101:1725-1729 |
ISSN: | 1460-2105 0027-8874 |
Popis: | Although estrogen receptor-alpha (ER) [corrected] is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ER-positive [corrected] breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ER [corrected] at serine-118 (ER alpha S118-P) is required for tamoxifen-mediated inhibition of ER-induced [corrected] 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), a statistically significant difference (P for interaction = .037). ER alpha 118-P was not associated with recurrence-free survival among untreated patients. Thus, ER alpha S118-P expression appears to be associated with response to tamoxifen. [corrected] |
Databáze: | OpenAIRE |
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