A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression.

Nathalie Reix,Stéphanie Delpous,Jean-Pierre Bellocq,Sébastien Molière,Karl Neuberger,Anthony Sevrin,Marie-Pierre Chenard,Charlotte Malina,Catherine Tomasetto,Carole Mathelin

doi:10.1007/s10549-016-4000-z

Abstract

PurposeWe explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression.MethodsWe prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up.ResultsElevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6–113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2–5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort.ConclusionsHER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cancer.

Highlights

About 15–20 % breast carcinomas have an overexpression of human epidermal growth factor receptor-2 (HER2) [1]
Purpose We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression
We considered that HER2/ECD level was consistent with metastasis progression when the increase between the result obtained 3 months before imaging and the result obtained just before imaging was at least 10 % or when the level remained elevated

Summary

Introduction

About 15–20 % breast carcinomas have an overexpression of human epidermal growth factor receptor-2 (HER2) [1]. This overexpression has been associated with a more aggressive disease, a poor clinical prognosis and the therapeutic success of trastuzumab [2]. A wide range of studies over the last 20 years reports that high HER2/ECD levels detected in the serum are associated with tumor aggressiveness, a less positive prognosis, and disease progression [6, 7]. Elevated HER2/ ECD levels may represent a subgroup of HER2-positive tumors with a higher level of HER2 cleavage that is associated to a more aggressive clinical course. HER2/ECD could be a biomarker that helps identify this subgroup of tumor and improve the risk stratification

Methods

Results

Discussion

Conclusion