• Clin Cancer Res · Jul 2018

    Randomized Controlled Trial

    p95HER2 Methionine 611 Carboxy-Terminal Fragment Is Predictive of Trastuzumab Adjuvant Treatment Benefit in the FinHer Trial.

    • Jeff Sperinde, Weidong Huang, Aki Vehtari, Ahmed Chenna, Pirkko-Liisa Kellokumpu-Lehtinen, John Winslow, Petri Bono, Yolanda S Lie, Christos J Petropoulos, Jodi Weidler, and Heikki Joensuu.
    • Monogram Biosciences, Inc., Laboratory Corporation of America Holdings, South San Francisco, California. sperinj@labcorp.com.
    • Clin Cancer Res. 2018 Jul 1; 24 (13): 3046-3052.

    AbstractPurpose: Expression of p95HER2 (p95), a truncated form of the HER2 receptor, which lacks the trastuzumab binding site but retains kinase activity, has been reported as a prognostic biomarker for poor outcomes in patients with trastuzumab-treated HER2-positive metastatic breast cancer. The impact of p95 expression on trastuzumab treatment efficacy in early HER2-positive breast cancer is less clear. In the current study, p95 was tested as a predictive marker of trastuzumab treatment benefit in the HER2-positive subset of the FinHer adjuvant phase III trial.Experimental Design: In the FinHer trial, 232 patients with HER2-positive early breast cancer were randomized to receive chemotherapy plus 9 weeks of trastuzumab or no trastuzumab treatment. Quantitative p95 protein expression was measured in formalin-fixed paraffin-embedded samples using the p95 VeraTag assay (Monogram Biosciences), specific for the M611 form of p95. Quantitative HER2 protein expression was measured using the HERmark assay (Monogram Biosciences). Distant disease-free survival (DDFS) was used as the primary outcome measure.Results: In the arm receiving chemotherapy only, increasing log10(p95) correlated with shorter DDFS (HR, 2.0; P = 0.02). In the arm receiving chemotherapy plus trastuzumab (N = 95), increasing log10(p95) was not correlated with a shorter DDFS. In a combined analysis of both treatment arms, high breast tumor p95 content was significantly correlated with trastuzumab treatment benefit in multivariate models (interaction P = 0.01).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. Clin Cancer Res; 24(13); 3046-52. ©2018 AACR.©2018 American Association for Cancer Research.

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