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.
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Authors | Bryce P Portier, Eugen C Minca, Zhen Wang, Christopher Lanigan, Aaron M Gruver, Erinn Downs-Kelly, G Thomas Budd, Raymond R Tubbs |
Journal | Oncotarget
(Oncotarget)
Vol. 4
Issue 10
Pg. 1662-72
(Oct 2013)
ISSN: 1949-2553 [Electronic] United States |
PMID | 24091566
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- ERBB4 protein, human
- ErbB Receptors
- Receptor, ErbB-4
- Trastuzumab
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Topics |
- Adult
- Algorithms
- Antibodies, Monoclonal, Humanized
(therapeutic use)
- Antineoplastic Agents
(therapeutic use)
- Breast Neoplasms
(drug therapy, enzymology, pathology)
- Chemotherapy, Adjuvant
- ErbB Receptors
(analysis, biosynthesis)
- Female
- Humans
- Immunohistochemistry
- Middle Aged
- Neoadjuvant Therapy
- Neoplasm Invasiveness
- Prognosis
- Receptor, ErbB-4
- Trastuzumab
- Treatment Outcome
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