Loss of B-cell translocation gene 2 expression in estrogen receptor-positive breast cancer predicts tamoxifen resistance.
Bottom Line: To determine if BTG2 expression modifies tamoxifen efficacy, a cohort of 60 patients treated with adjuvant tamoxifen monotherapy was analyzed.We found that increased BTG2 expression showed better clinical survival and was the only independent prognostic factor for disease-free survival (hazard ratio, 0.691; 95% confidence interval, 0.495-0.963; P = 0.029).Consistent with this observation, tamoxifen significantly suppressed the growth ratio, tumor weight and Ki-67 expression in BTG2 expressing breast cancer xenografts in mice.
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.Show MeSH
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Mentions: After 21 days of treatment there was no significant difference in tumor volumes between treated and untreated tumors in animals bearing control tumors (n = 11) or mice treated with tetracycline alone (n = 10), suggesting that BTG2 expression did not affect tumor growth in this xenograft model (Fig4a). Tamoxifen treatment alone, without tetracycline (n = 10), significantly decreased the tumor growth ratio compared with the negative control (P = 0.009). Remarkably, the tumor growth ratio was strongly suppressed, to a statistically significant level, with concomitant administration of tetracycline and tamoxifen (n = 8) in comparison with tamoxifen monotherapy (P = 0.044; Fig4a). Correspondingly, tamoxifen treatment in the context of BTG2 expression significantly reduced the tumor weight compared with tamoxifen treatment alone (P = 0.034; Fig4b). Concomitant administration of tamoxifen and tetracycline led to decreased Ki-67 expression compared with the control group (P = 0.009) or the group treated with tamoxifen alone (P = 0.039; Fig.4c,d).
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.