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

Breast Cancer Res Treat. 2016 Nov;160(2):249-259. doi: 10.1007/s10549-016-4000-z. Epub 2016 Oct 5.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Female
  • Gene Expression*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Protein Domains*
  • Receptor, ErbB-2 / blood*
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / genetics*


  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2