Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99

Abstract

Abstract Background The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2–24 h; at 3 weeks; at first response evaluation (8–9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2ECD levels were stable within 24 h after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs = 0.39, P 35 ng/ml) had the worst overall survival (P = 0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values ( 20%. Conclusions Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy. Trial registration Registration Number by ClinicalTrials.gov: NCT00004935, Trial number: SAKK22/99. Registered on 27 January 2003.

Keywords

• HER2+ breast cancer
• Plasma HER2ECD levels
• Baseline
• Trastuzumab
• Sequential therapy
• Upfront combined therapy