Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 101, Issue 24, Pages 1725-1729Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djp412
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Funding
- Top Institute Pharma
- Pink Ribbon/A Sister's Hope
- Swedish Cancer Society
- Malmo University Hospital Research Cancer Funds
- Breakthrough Breast Cancer
- Marie Curie Transfer of Knowledge Industry-Academia Partnership research program
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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.
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