High serum HER2 extracellular domain levels: correlation with a worse disease-free survival and overall survival in primary operable breast cancer patients.

PURPOSE: High serum human epidermal growth factors receptor-2 (HER2) extracellular domain (ECD) has been identified as an independent prognostic indicator of poor prognosis in metastatic breast cancer. However, its prognostic value in primary operable breast cancer was still controversial. We aim to investigate the correlation between serum HER2 ECD levels and tissue HER2 status, the association between serum HER2 ECD levels and clinicopathological characteristics, and their impacts on disease-free survival (DFS) and overall survival (OS) in primary operable breast cancer. METHODS: Two hundred and fifty-two primary operable breast cancer patients pretreated from 2002 to 2009 in Sun Yat-Sen University Cancer Center were enrolled in this study. Serum HER2 ECD was measured by chemiluminescent assay, and tissue HER2 status was accessed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) assay. RESULTS: There was a significant correlation between serum HER2 ECD levels and HER2 tissue status (P < 0.001, R = 0.36). High serum HER2 ECD levels (≥15 ng/mL) were significantly associated with age (≥35 years) (P = 0.028), postmenopausal status (P < 0.001), stage III (P < 0.001), tumor size (≥2 cm) (P < 0.001), lymph node involvement (P < 0.001), negative estrogen receptor (P = 0.005), and progesterone receptor status (P = 0.001). Multivariate analysis showed that high serum HER2 ECD level was an independent prognostic factor of worse DFS (P = 0.014) and OS (P = 0.014) in primary operable breast cancer patients. CONCLUSION: Serum HER2 ECD level can reflect tissue HER2 status and can be an independent prognostic indicator for primary operable breast cancer patients.