Estrogen Receptor-alpha Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer
2009 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, Vol. 101, no 24, 1725-1729 p.Article in journal (Refereed) Published
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-52864DOI: 10.1093/jnci/djp412OAI: oai:DiVA.org:liu-52864DiVA: diva2:285791