Postoperatively Elevated Serum Level Of HER2 Extracellular Domain Is Related With Lymph Node Metastasis of Primary Breast Cancer in a Population Based Study

HER2 is a member of the tyrosine kinase receptor ErbB oncogene family overexpressed in 25% of human breast carcinomas. Proteo-lytic cleavage results in release of the extracellular domain (ECD) and formation of a truncated membrane-bound fragment. We studied the relation between postoperative HER2 ECD serum levels and clinical parameters in a population-based sample of 273 women with primary breast cancer from Germany. The serum concentration of HER2 ECD as determined by using an ELISA ranged from 1268 HNU/ml to 63355 HNU/ml (median: 2899 HNU/ml). The mean decrease was 32 HNU/ml per postoperative day. In bivariate analyses, age >50, postmenopausal status, degree of lymph node involvement, tumor staging and tumor markers CEA and CA15.3 were significantly related with a HER2 ECD level in the upper tertile of the distribution. No association with HER2 ECD concen-tration was found for tumor size, M-staging, histological type and grading, estrogen receptor status and progesterone receptor status. In multivariate analyses, metastasis staging (regional: OR 2.0; 95%- CI 1.1–3.7; distant: OR 5.0; 95%-CI 0.5–49.5), degree of axillary lymph node involvement (1–3 lymph nodes: OR 1.9; 95%-CI 0.9–3.9; >3 lymph nodes: OR 2.9; 95%-CI 1.2–6.8) as well as age >50 (OR 2.1; 95%-CI 1.0- 4.1) and elevated tumor marker CEA (OR 6.8; 95%-CI 1.3–34.8) were significant predictors for elevated HER2 ECD serum concentration. Elevated HER2 ECD after initial surgery was related to extent of lymph node involvement and may help to identify patients who could benefit from HER2 targeted (adjuvant) therapy.