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

Nathalie Reix (1, 2, 3) , Charlotte Malina (3) , Marie Pierrette Chenard (3) , Jean-Pierre Bellocq (3) , Stéphanie Delpous (4) , Sébastien Molière (3) , Anthony Sevrin (5) , Karl Neuberger (5) , Catherine Tomasetto (4) , Carole Mathelin (4, 3)

1 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
2 FMTS - Fédération de Médecine Translationnelle de Strasbourg
3 HUS - Les Hôpitaux Universitaires de Strasbourg
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 The State of the Art AI company - Quantmetry [Paris]

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

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

Domaines: Cancer; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Nathalie Reix, Charlotte Malina, Marie Pierrette Chenard, Jean-Pierre Bellocq, Stéphanie Delpous, et al.. A prospective study to assess the clinical utility of serum HER2 extracellular domain in breast cancer with HER2 overexpression. Breast Cancer Research and Treatment, 2016, 160 (2), pp.249-259. ⟨10.1007/s10549-016-4000-z⟩. ⟨hal-03636043⟩