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

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.