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08.02.2020 | Original Article – Cancer Research | Ausgabe 3/2020 Open Access

Journal of Cancer Research and Clinical Oncology 3/2020

New HER2-negative breast cancer subtype responsive to anti-HER2 therapy identified

Journal of Cancer Research and Clinical Oncology > Ausgabe 3/2020
Ian A. MacNeil, David J. Burns, Benjamin E. Rich, Sajjad M. Soltani, Samantha Kharbush, Nicole G. Osterhaus, Brian F. Sullivan, Douglas M. Hawkins, Jodie R. Pietruska, Lance G. Laing
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The online version of this article (https://​doi.​org/​10.​1007/​s00432-020-03144-7) contains supplementary material, which is available to authorized users.

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HER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient’s live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies.


The CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2−/HSFs+).


HER2−/HSFs+ breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+ and HER2− cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI = 17–32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2−/HSFs+ patient population.


The CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+ population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20–25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.

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