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Breast Cancer Res Treat. 2016 Nov;160(2):249-259. Epub 2016 Oct 5.

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

Author information

1
ICube UMR 7357, Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France. nathalie.reix@chru-strasboug.fr.
2
Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France. nathalie.reix@chru-strasboug.fr.
3
Unité de Sénologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
4
Service de Pathologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
5
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France.
6
Department of Imaging, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
7
Quantmetry, 55 rue La Boetie, 75008, Paris, France.

Abstract

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.

METHODS:

We 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.

RESULTS:

Elevated 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.

CONCLUSIONS:

HER2/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.

KEYWORDS:

Breast cancer; Extracellular domain ECD; HER2 positive; Monitoring; Prognosis factor; Trastuzumab

PMID:
27709352
PMCID:
PMC5065601
DOI:
10.1007/s10549-016-4000-z
[Indexed for MEDLINE]
Free PMC Article

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