Prognostic and predictive impact of the HER-2/ neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer.
BACKGROUND: The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated. METHODS: In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46). RESULTS: HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006). CONCLUSION: In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.
BACKGROUND: The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated. METHODS: In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46). RESULTS: HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006). CONCLUSION: In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.