title: A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression.
abstract: 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 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: ICube UMR 7357, Université de Strasbourg/CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France. nathalie.reix@chru-strasboug.fr.|Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France. nathalie.reix@chru-strasboug.fr.
authors.forename: Nathalie
authors.identifier: 0000-0003-0434-2895
authors.initials: N
authors.lastname: Reix
authors.affiliation: Unité de Sénologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Malina
authors.affiliation: Service de Pathologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Service de Pathologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bellocq
authors.affiliation: 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.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Delpous
authors.affiliation: Department of Imaging, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Molière
authors.affiliation: Quantmetry, 55 rue La Boetie, 75008, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Sevrin
authors.affiliation: Quantmetry, 55 rue La Boetie, 75008, Paris, France.
authors.forename: Karl
authors.initials: K
authors.lastname: Neuberger
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomasetto
authors.affiliation: Unité de Sénologie, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098, Strasbourg, France.|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.
authors.forename: Carole
authors.initials: C
authors.lastname: Mathelin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D000072417:Protein Domains; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000737:chemistry / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Extracellular domain ECD; HER2 positive; Monitoring; Prognosis factor; Trastuzumab