Serum Levels of HER2 ECD Can Determine the Response Rate to Low Dose Oral Cyclophosphamide and Methotrexate in Patients with Advanced Stage Breast Carcinoma

Abstract

Background: The proto-oncogene HER2/neu encodes for a transmembrane receptor protein whose overexpression in breast cancer may be associated with poor prognosis. Its extracellular domain (HER2 ECD) can be shed into the circulation. The purpose of this study was to evaluate the predictive value of HER2 ECD in patients with advanced breast cancer. Patients and Methods: HER2 ECD was determined in 39 patients with advanced breast cancer, treated with oral cyclophosphamide and methotrexate (CM) at low doses. HER2 ECD levels were determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of chemotherapy, when all the patients were reevaluated. Results: Based on the response to chemotherapy, the patients were divided into two groups: progressive disease (PD, 14 patients) and patients with clinical benefit (CB; i.e. patients with stable or responsive disease, 25 patients). The patients with PD had a mean baseline value of HER2 ECD of 38.3±69.2 ng/ml, while the group of CB showed lower levels (9.2±2.3 ng/ml, p<0.05). After 2 months, the mean value of HER2 ECD in the PD group increased to 71.6±146 ng/ml, while in the other group the levels did not change (9.7±2.4 ng/ml). At follow-up, significant differences were noted in both the time to progression and overall survival, with patients with increased levels of HER2 ECD at baseline (≥15 ng/ml) showing a worse clinical outcome. Conclusion: Increased pretreatment levels of HER2 ECD identify a subset of patients with more aggressive tumors and less response to CM chemotherapy. During therapy, increasing levels of HER2 ECD are associated with disease progression.