Research Papers:
HER4 expression status correlates with improved outcome in both neoadjuvant and adjuvant Trastuzumab treated invasive breast carcinoma
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2229 views | HTML 2861 views | ?
Abstract
Bryce P Portier1, Eugen C Minca2, Zhen Wang2, Christopher Lanigan2, Aaron M Gruver2, Erinn Downs-Kelly2, G Thomas Budd3, and Raymond R Tubbs2
1 Department of Pathology and Genomic Medicine, Houston Methodist, Houston, TX
2 Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH
3 Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
Correspondence:
Bryce P. Portier, email:
Keywords: Breast carcinoma, HER2, HER4, Immunohistochemistry, RT-qPCR, Trastuzumab, H-Score
Received: July 31, 2013 Accepted: August 24, 2013 Published: August 26, 2013
Abstract
Prognostic and predictive markers utilized in invasive breast carcinoma are limited and include ER, PR, Ki67, and ERBB2 (HER2). In the case of HER2, over-expression or amplification serves as eligibility for anti-HER2 based therapy, including trastuzumab (Herceptin®, Genentech). While clinical trials have shown trastuzumab improves overall survival and time to progression, an individual’s response to anti-HER2 based therapy is highly variable. This suggests that, in a “uniform” HER2 positive population, additional markers could help in predicting patient outcome to therapy. Here we utilized a recently validated high-specificity HER4 antibody (E200) and generated a standard clinical HER4 scoring algorithm (HER4 H-Score) utilizing two breast carcinoma cohorts: 1) patients receiving neoadjuvant trastuzumab (n=47) and 2) patients receiving trastuzumab for metastatic disease (n=33). Our HER4 H-Score showed significant correlation with high sensitivity RT-qPCR performed on matched patients (p=<0.0001). In addition, patients with HER2/HER4 co-over-expression status showed a significant delay in development of metastasis after neo-adjuvant trastuzumab therapy (p= 0.04) and showed a significant improvement in progression free survival after adjuvant trastuzumab therapy (p=0.03). These findings suggest HER4 IHC, used in conjunction with a standard HER2 testing algorithm, could aid in predicting clinical outcome and help identify patients likely to show improved response to trastuzumab therapy.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1232