Abstract 7634: HER2 extracellular domain in serum samples from HER2+ metastatic breast cancer patients as a potential biomarker of progression-free survival

Abstract Introduction: The detection of serum biomarkers holds potential for non-invasive methods for early cancer detection, monitoring of disease progression, and assessment of treatment responses leading to earlier interventions that may significantly improve patient outcomes. Human epidermal growth factor receptor 2 (HER2) overexpression plays a key role in the prognosis of HER2+ breast cancer (BC). While HER2 is well-established as a cell surface marker, its soluble extracellular domain (ECD) in serum has gained attention as a potential prognostic biomarker. Elevated levels of HER2 ECD (>15ng/ml) have been associated with a poor outcome. However only a small percentage of primary BC patients have levels of HER2 ECD >15ng/ml. Research has suggested that HER2 targeted therapies can influence the rate of HER2 ECD shedding. Therefore, this study aimed to explore the association between circulating HER2 ECD levels with progression-free survival (PFS) and overall survival (OS) in patients with metastatic HER2+ BC. Methods: Matched Pre and post treatment serum samples (n=25) from BC patients enrolled in TH V THL (ICORG (CTRIAL-IE) 11-10/NCT01526369) clinical trial were assessed. Human ErbB2 (HER2) ELISA Kit (Invitrogen) was used to detect levels of soluble HER2 ECD in the serum. Serum levels were stratified as Low (<300pg/ml n=5), Intermediate (300-700pg/ml n=10) or High (>700pg/ml n=10). Patient data correlation was used to assess PFS and OS, Kaplan-Meier survival curves were constructed based on the serum levels of HER2 ECD. Significance p values were determined using log-rank (Mantel-Cox) test. Results: Levels of HER2 ECD detected (94-1730pg/ml) did not exceed 15ng/ml for any sample. There was no significant difference in HER2 ECD levels between treatment arms (TH vs. THL) for PFS (p=0.4685) or OS (p=0.1376). There was no change between the pre and post treatment HER2 ECD serum levels in the samples tested (p=0.344). However, when pre-treatment samples were stratified based on Low, Intermediate or High HER2 ECD levels, there was a significant increase in PFS for patients in the High cohort. Median PFS increased from 8.31 months in the Low cohort to 13.57 months in the Intermediate cohort. The median PFS increased further to 22.24 months in the High cohort (Log rank p=0.0197). The same parameters were applied for the analysis of OS, which also improved as the level of HER2 ECD increased. Median OS increased from 35.19 months (Low) to 68.7 months (Intermediate), with a Median OS not reached for the High cohort (Log rank p=0.077). Conclusions: Patients with HER2 ECD levels above 700pg/ml display a survival advantage in this limited study. Further validation and prospective studies are warranted to fully establish the clinical utility of HER2 ECD as a biomarker in metastatic HER2+ BC. Citation Format: Debbie O'Reilly, Marc Nolan, Ausra Teiserskiene, Bryan T. Hennessy, John Crown, Denis M. Collins. HER2 extracellular domain in serum samples from HER2+ metastatic breast cancer patients as a potential biomarker of progression-free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7634.