Paper Info
Title
Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors
Abstract
Human epidermal growth factor receptor 2 amplified (HER2+) breast cancer is common and aggressive. Trastuzumab is a targeted therapy to the HER2 cell surface receptor and has greatly improved prognosis for HER2+ breast cancer patients, but trastuzumab-resistance is a significant problem. Few biomarkers of trastuzumab resistance of response have been found, and there has been tremendous difficulty identifying in vitro biomarkers that transfer to the in vivo HER2+ breast cancer setting. We identified gene expression signatures of trastuzumab-response and trastuzumab-resistance in HER2+ breast cancer cell lines across 24-hour exposure to trastuzumab. A set of 180-genes changed significantly in a trastuzumab-sensitive HER2+ cell line (BT474) and 58 genes changed significantly across treatment in a trastuzumab-resistant HER2+ cell line (UACC812). To demonstrate that these signatures have clinical relevance, we applied them in vivo to gene expression profiles from early stage HER2+ breast tumors treated with a single dose of trastuzumab. We found that the BT474 trastuzumab-responsive signature was enriched among the changes in expression across treatment for responsive patients. The expression change for the BT474 signature genes was also able to partially cluster responsive and resistant breast tumors by outcome. A subset of the UACC812 trastuzumab-resistance signature was also enriched in the differential between responsive and resistant tumors prior to trastuzumab treatment. These results show for the first time that cell line-derived gene signatures can be useful in identifying whether breast cancer patients will ultimately benefit from trastuzumab treatment. This approach might one day be applied to enhance clinical treatment decisions.
Year
DOI
Venue
2011
10.1145/2147805.2147867
BCB
Keywords
DocType
Citations 
breast cancer cell line,trastuzumab-sensitive her2,early stage her2,breast tumor,breast cancer,vivo her2,trastuzumab-resistant her2,cell line,her2 cell surface receptor,breast cancer setting,breast cancer patient,trastuzumab exposure,drug resistance,gene expression
Conference
0
PageRank 
References 
Authors
0.34
0
9
Name
Order
Citations
PageRank
Emmett Sprecher11488.34
Sudipa Sarkar200.34
Steven H Kleinstein39516.45
Murli Narayan400.34
Eric Winer500.34
David Tuck6143.49
Kimberly Lezon-Geyda700.34
Ian Krop800.34
Lyndsay Harris900.34