Oncotarget

Research Papers:

A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity

Yao Huang, David J Burns, Benjamin E Rich, Ian A MacNeil, Abhijit Dandapat, Sajjad M. Soltani, Samantha Myhre, Brian F Sullivan, Leo T Furcht, Carol A Lange, Sara A Hurvitz, Lance G Laing _

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Oncotarget. 2016; 7:78577-78590. https://doi.org/10.18632/oncotarget.12480

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Abstract

Yao Huang1, David J Burns1, Benjamin E Rich1, Ian A MacNeil1, Abhijit Dandapat1, Sajjad M. Soltani1, Samantha Myhre1, Brian F Sullivan1, Leo T Furcht2, Carol A Lange3, Sara A Hurvitz4, Lance G Laing1

1Celcuity LLC, Minneapolis, MN 55446, USA

2Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA

3Division of Hematology, Oncology and Transplantation, Departments of Medicine and Pharmacology and The Masonic Cancer Center, Minneapolis, MN 55455, USA

4Division of Hematology/Oncology and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA

Correspondence to:

Lance G Laing, email: LLaing@Celcuity.com

Keywords: HER2 negative, HER2 signaling, targeted therapy, CELx HSP test, tumor primary cells

Received: June 17, 2016     Accepted: September 29, 2016     Published: October 05, 2016

ABSTRACT

The results of clinical trials evaluating the efficacy of HER2 inhibitors in patients with breast cancer indicate that the correlation between HER2 receptor levels and patient outcomes is as low as 50%. The relatively weak correlation between HER2 status and response to HER2-targeting drugs suggests that measurement of HER2 signaling activity, rather than absolute HER2 levels, may more accurately diagnose HER2-driven breast cancer. A new diagnostic test, the CELx HER2 Signaling Profile (CELx HSP) test, is demonstrated to measure real-time HER2 signaling function in live primary cells. In the present study, epithelial cells extracted fresh from breast cancer patient tumors classified as HER2 negative (HER2, n = 34 of which 33 were estrogen receptor positive) and healthy subjects (n = 16) were evaluated along with reference breast cancer cell lines (n = 19). Live cell response to specific HER2 agonists (NRG1b and EGF) and antagonist (pertuzumab) was measured. Of the HER2 breast tumor cell samples tested, 7 of 34 patients (20.5%; 95% CI = 10%–37%) had HER2 signaling activity that was characterized as abnormally high. Amongst the tumor samples there was no correlation between HER2 protein status (by cell cytometry) and HER2 signaling activity (hyperactive or normal) (Regression analysis P = 0.144, R2 = 0.068). One conclusion is that measurement of HER2 signaling activity can identify a subset of breast cancers with normal HER2 receptor levels with abnormally high levels of HER2 signaling. This result constitutes a new subtype of breast cancer that should be considered for treatment with HER2 pathway inhibitors.

Author Information

Yao Huang

David J Burns

Benjamin E Rich

Ian A MacNeil

Abhijit Dandapat

Sajjad M. Soltani

Samantha Myhre

Brian F Sullivan

Leo T Furcht

Carol A Lange

Sara A Hurvitz

Lance G Laing
Primary Contact  _


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