High p95HER2/HER2 ratio associated with poor outcome in trastuzumab-treated HER2-positive metastatic breast cancer ncctg N0337 and NCCTG 98-32-52 (Alliance)

Saranya Chumsri, Jeff Sperinde, Heshan Liu, Joseph Gligorov, Jean Philippe Spano, Martine Antoine, Alvaro Moreno Aspitia, Winston Tan, John Winslow, Christos J. Petropoulos, Ahmed Chenna, Michael Bates, Jodi Marie Weidler, Weidong Huang, Amylou Dueck, Edith A. Perez

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose: p95HER2 is a truncated form of HER2 that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials. Experimental Design: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples. Results: In the multivariate model, increasing total HER2 level was significantly associated with longer (OS; HR, 0.33; P = 0.002) and decreasing p95HER2 level was significantly associated with longer OS (HR, 4.2; P = 0.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR, 0.57; P = 0.04), whereas p95HER2 level was not (HR, 1.7; P = 0.25). However, there was a positive association between p95HER2 and total HER2 expression levels (R2 = 0.48; P < 0.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR, 1.7; P = 0.04) and OS (HR, 2.8; P = 0.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR, 1.8; P= 0.06) and OS (HR, 2.3; P= 0.02). Conclusions: A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted.

Original languageEnglish (US)
Pages (from-to)3053-3058
Number of pages6
JournalClinical Cancer Research
Volume24
Issue number13
DOIs
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chumsri, S., Sperinde, J., Liu, H., Gligorov, J., Spano, J. P., Antoine, M., Aspitia, A. M., Tan, W., Winslow, J., Petropoulos, C. J., Chenna, A., Bates, M., Weidler, J. M., Huang, W., Dueck, A., & Perez, E. A. (2018). High p95HER2/HER2 ratio associated with poor outcome in trastuzumab-treated HER2-positive metastatic breast cancer ncctg N0337 and NCCTG 98-32-52 (Alliance). Clinical Cancer Research, 24(13), 3053-3058. https://doi.org/10.1158/1078-0432.CCR-17-1864