Send to

Choose Destination
Clin Cancer Res. 2018 Jul 1;24(13):3046-3052. doi: 10.1158/1078-0432.CCR-17-3250. Epub 2018 Mar 13.

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

Author information

Monogram Biosciences, Inc., Laboratory Corporation of America Holdings, South San Francisco, California.
Monogram Biosciences, Inc., Laboratory Corporation of America Holdings, South San Francisco, California.
Helsinki Institute for Information Technology HIIT, Department of Computer Science, Aalto University, Finland.
Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland.
Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Monogram Biosciences, currently Cepheid, Sunnyvale, California.
Department of Oncology, Helsinki University Hospital & Helsinki University, Helsinki, Finland.


Purpose: 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.

Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center