The predictive and monitoring value of serum HER2/NEU in breast cancer under trastuzumab therapy.

Abstract

In breast cancer, the Human Epidermal growth factor Receptor 2 (HER2) is associated with worst prognosis in all stages of the disease, and it is specifically targeted by a monoclonal antibody (trastuzumab). Nevertheless, the different response rates observed have increased the search for better predictive markers. Elevated levels of the extracellular domain of HER2/neu in the serum have been associated with the clinical outcome of breast cancer patients.The authors proposed to analyze serum HER2/neu in breast cancer patients, under treatment with trastuzumab, in monotherapy or associated with another systemic therapy, either in adjuvant or metastatic setting, in order to evaluate its role as prognostic, predictive and monitoring factor. From March 2007 to May 2008, 173 serum samples from 43 patients were analysed, corresponding to the beginning of the treatment of trastuzumab and 3/3 months afterwards. Serum HER2/neu levels were measured with ADVIA Centaur(®) immunoassay and levels > 15 ng/mL were defined as elevated, according to previous reports.Elevated baseline serum levels were found to be associated with a worst overall survival (p = 0,003). In the metastatic setting, baseline HER2/neu serum levels were not associated with response rate to trastuzumab. However, when we analyzed the variations in HER2/neu serum levels between the response evaluation date and the first measurement, we observed that patients whose serum levels declined showed significantly higher objective response compared with patients with stable or elevated serum values (p = 0,001). Moreover, monitoring early changes in serum levels (three months) could also predict the probability of response to trastuzumab-based treatment (p = 0,007).The use of this predictive potential could not only focus and tailor treatment individually but also adapt to economic needs.