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Amplified in Breast Cancer 1 in Human Epidermal Growth Factor Receptor–Positive Tumors of Tamoxifen-Treated Breast Cancer Patients

Authors' Affiliations: ¹ Endocrine Cancer Group, Section of Surgical and Translational Research and ² Department of Pathology, Glasgow University, Glasgow Royal Infirmary, Glasgow, United Kingdom and ³ DAKO Denmark A/S, Glostrup, Denmark

Requests for reprints: John M.S. Bartlett, Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, United Kingdom. Phone: 131-777-3584; Fax: 131-777-3520; E-mail: John.Bartlett{at}ed.ac.uk.

Purpose: Amplified in breast cancer 1 (AIB1) 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- (ER-). The present study was carried out to test the hypothesis that AIB1 protein expression and/or gene amplification mediates tamoxifen resistance in breast cancer.

Experimental Design: Immunohistochemistry using AIB1 antibody and fluorescence in situ hybridization using probes specific for AIB1 and chromosome 20 was done on 402 ER-–positive tamoxifen-treated breast cancers.

Results: AIB1 overexpression was not associated with relapse during treatment with tamoxifen. In contrast, high AIB1 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]. AIB1 gene amplification was observed in 18 of 362 (5%) patients. High AIB1 gene copy number had no effect on overall or disease-free survival.

Conclusions: Data presented here support a role for AIB1 expression on relapse during tamoxifen treatment in hormone-responsive HER-expressing clinical breast cancers and support clinical evidence, suggesting a cross-talk between ER- and growth factor receptor pathways through changes in expression of specific coactivator proteins, such as AIB1. 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.

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