Comparison of Pre- and Postsurgical Concentrations of Blood HER-2 mRNA and HER-2 Extracellular Domain Reflects HER-2 Status in Early Breast Cancer

The HER-2 gene (HER-2/neu or c-erbB-2) encodes an 185-kDa transmembrane glycoprotein that is a member of the type I family of growth factor receptors. HER-2 is constitutively activated by overexpression and contributes to cell growth, angiogenesis, survival, and metastasis (1). The assessment of HER-2 status in breast carcinomas provides valuable prognostic and predictive information. Immunohistochemistry, fluorescence in situ hybridization, chromosomal in situ hybridization, and quantitative reverse transcription-PCR (RT-PCR) may be used for this purpose. Other approaches have been proposed for the assessment of HER-2 status in peripheral blood, including evaluating either circulating HER-2 extracellular domain (ECD) or nucleated cell-associated HER-2 mRNA. Some studies have indicated that circulating ECD/HER-2 is frequently increased in metastatic disease (2)(3)(4). In addition, high concentrations of ECD/HER-2 are associated with cancer aggressiveness (5) and predict response to trastuzumab (6)(7)(8) and antiestrogen (4) therapies in advanced breast cancer. Recently, Martin et al. (9), using an array to assess circulating mRNA, pointed out that HER-2 mRNA was generally low in the blood of healthy individuals but was increased in 31% of patients with untreated invasive breast cancer. Almost all of these studies evaluated blood markers in patients with advanced or metastatic breast cancer using a single presurgical sample.Our study included 40 consecutive patients (median age, 58 years; range, 29–80 years) undergoing surgery for early breast cancer. Patients did not receive any systemic therapy before surgery and provided informed consent for the study. According to tumor size, 28 patients were classified as T1, whereas the remaining 12 were T2 or T3. Twenty-two were node negative, and 35 were positive for estrogen receptors. From each patient, we collected 12 mL of venous blood in EDTA tubes and divided the blood into two 5-mL aliquots. The first was centrifuged, and the plasma …