Amplified in breast cancer 1 in human epidermal growth factor receptor-positive tumors of tamoxifen-treated breast cancer patients

Purpose: Amplified in breast cancer 1 (AlB1) is a member of the p160/steroid receptor coactivators family and is involved in estrogen - dependent gene transcription by reducing the antagonistic activity of tamoxifen-bound estrogen receptor-alpha (ER-alpha). The present study was carried out to test the hypothesis that AlB1 protein expression and/or gene amplification mediates tamoxifen resistance in breast cancer. Experimental Design: Immunohistochemistry using AlB1 antibody and fluorescence in situ hybridization using probes specific for AlB1 and chromosome 20 was done on 402 ER-alpha.-positive tamoxifen-treated breast cancers. Results: AlB1 overexpression was not associated with relapse during treatment with tamoxifen. In contrast, high AlB1 expression in patients with human epidermal growth factor receptor (HER) 2- and HER3-overexpressing tumors or tumors expressing one or more of HER1, HER2, or HER3 (HER1-3 positive) was associated with an increased risk of relapse on tamoxifen [hazard ratio, 2.20; 95% confidence interval, 1.07-3.52 (P = 0.0416); hazard ratio, 2.42; 95% confidence interval, 1.32-4.43 (P = 0.0030), respectively]. AlB1 gene amplification was observed in 18 of 362 (5%) patients. High AlB1 gene copy number had no effect on overall or disease-free survival. Conclusions: Data presented here support a role for AlB1 expression on relapse during tamoxifen treatment in hormone-responsive HER-expressing clinical breast cancers and support clinical evidence, suggesting a cross-talk between ER-alpha and growth factor receptor pathways through changes in expression of specific coactivator proteins, such as AlB1. This study highlights the potential that tumor profiling, using multiple markers of treatment response, may improve patient selection for endocrine treatment, such as tamoxifen or aromatase inhibitors.