p95HER2 methionine 611 carboxy-terminal fragment is predictive of trastuzumab adjuvant treatment benefit in the FinHer trial

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 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 HER2-positive early breast cancer patients 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=.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=.01). Conclusions: p95 expression levels were prognostic in the chemotherapy-alone arm and predictive of trastuzumab treatment benefit in FinHer. These results warrant further investigation of p95 as a predictive marker of trastuzumab treatment benefit in the adjuvant setting.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Go0niF