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

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From: Journal of the National Cancer Institute(Vol. 101, Issue 24)
Publisher: U.S. National Cancer Institute
Document Type: Author abstract
Length: 208 words

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Abstract :

Although estrogen receptor-[alpha] (ER[alpha]) is a marker used to identify breast cancer patients most likely to benefit from endocrine theraphy, 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 AIIred 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. DOI: 10.1093/jnci/djp412

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Gale Document Number: GALE|A215513954