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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Breast Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1605120

Detection of serum HER2 in patients treated with neratinib or trastuzumab: analysis of the I-SPY TRIAL

Provisionally accepted
Mark HensleyMark Hensley1Justin LengfeldJustin Lengfeld2Steven StoeszSteven Stoesz2Michelle EdwardsMichelle Edwards2Franklin PassFranklin Pass2Gillian L HirstGillian L Hirst3Lamorna Brown-SwigartLamorna Brown-Swigart3Laura Van 'T VeerLaura Van 'T Veer3Laura J EssermanLaura J Esserman3Heather BeckwithHeather Beckwith4Douglas YeeDouglas Yee4,5*
  • 1Hensley Biostats, Seattle, United States
  • 2Martell Diagnostics Laboratories, Roseville, United States
  • 3University of California, San Francisco, San Francisco, California, United States
  • 4University of Minnesota Twin Cities, St. Paul, United States
  • 5Masonic Cancer Center, Medical School, University of Minnesota, Minneapolis, Minnesota, United States

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Purpose -Drugs targeting human epidermal growth factor receptor 2 (HER2) have fundamentally changed the way breast cancer is treated. Measurement of HER2 expression has become increasingly important with the approval of therapies targeting a HER2-low population. Further, predictive biomarkers of HER2 response would aid the clinical use of these drugs and a bloodbased assay of HER2 could provide important information for therapeutic options for patients.Methods -To evaluate serum HER2 (sHER2) as a potential biomarker for breast cancer response, we examined serum samples from patients treated with neratinib or trastuzumab combined with paclitaxel obtained from the I-SPY2 TRIAL neoadjuvant trial. This trial included both HER2-positive and HER2-negative/low tumors.Results -26% of patients with HER2 negative tumors had elevated sHER2 while 56% of the HER2positive patients had elevated sHER2. sHER2 levels declined with neoadjuvant therapy and most patients had a clinical response to therapy. However, sHER2 decline was not predictive of pathologic complete response.Conclusion -sHER2 was detected in patients with both HER2 tissue positive and negative tumors. Further study will be needed to determine if sHER2 associates with patients with tumors that are HER2-low or ultralow and if changes in sHER2 over time could predict response to HER2 targeted drugs.

Keywords: HER2, biomarkers, Neoadjuvant Therapy, Neratinib, trastuzumab

Received: 02 Apr 2025; Accepted: 27 Jun 2025.

Copyright: © 2025 Hensley, Lengfeld, Stoesz, Edwards, Pass, Hirst, Brown-Swigart, Van 'T Veer, Esserman, Beckwith and Yee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Douglas Yee, University of Minnesota Twin Cities, St. Paul, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material