NEW YORK (Reuters Health) Nov 25 - In premenopausal women with ER-positive breast cancer, high expression of serine-118-phosphorylated alpha estrogen receptors (ER-alpha-S118-P) is associated with an improved response to tamoxifen, European investigators report.
"Our study highlights the importance of assessing the functionality of a drug target," Dr. Goran Landberg at the University of Manchester, UK, and his associates write in the Journal of the National Cancer Institute published online on November 25.
About half of ER-alpha-positive breast carcinomas are resistant to tamoxifen. Until now, there have been no validated biomarkers that predict tamoxifen response in these tumors, although animal studies have indicated that ER-alpha-S118-P is required for the drug to work.
Dr. Landberg's group evaluated data from 239 premenopausal patients diagnosed with stage II, ER-alpha positive breast cancer in whom ER-alpha-S118-P status could be determined. The women had been randomly assigned to 2 years of adjuvant tamoxifen treatment or to no systemic treatment.
Immunohistochemical analysis revealed that 115 patients had low ER-alpha-S118-P expression and 124 had high expression.
In patients with high ER-alpha-S118-P expression, tamoxifen therapy was associated with a significant improvement in recurrence-free survival compared with no systemic treatment (23.7 vs 72.2 recurrences per 1000 person-years, hazard ratio = 0.36, p = 0.037).
On the other hand, tamoxifen therapy did not improve survival among patients with low ER-alpha-S118-P expression.
However, Dr. Landberg and associates caution, "Further investigations of the relationship between ER-alpha-S118-P status and survival in larger study populations are required before withholding tamoxifen treatment for certain patients can be recommended." They also recommend that a similar study be done among postmenopausal women.
J Natl Cancer Inst 2009.
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