Jeff Sperinde 1 , Weidong Huang 2 , Aki Vehtari 3 , Ahmed Chenna 2 , Pirkko-Liisa Kellokumpu-Lehtinen 4 , John Winslow 2 , Petri Bono 5 , Yolanda S Lie 2 , Christos J Petropoulos 2 , Jodi Weidler 6 , Heikki Joensuu 7 Show Affiliations »
Abstract
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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. ©2018 American Association for Cancer Research.
RCT Entities: Population
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Outcomes
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. ©2018 American Association for Cancer Research.
Entities: Chemical
Disease
Gene
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Year: 2018
PMID： 29535130 DOI： 10.1158/1078-0432.CCR-17-3250
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531