A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity
Metrics: PDF 637 views | HTML 498 views | ?
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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.