Serum EGFR and serum HER‐2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy

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Abstract
BACKGROUND. Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER‐2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER‐2/neu and serum EGFR in breast cancer patients treated with low‐dose chemotherapy. METHODS. Serum levels of HER‐2/neu (n = 135) and of EGFR (n = 113) were prospectively determined before the start of chemotherapy, after 2 months of treatment, and when progressive disease was diagnosed. RESULTS. Elevated (>15 ng/mL) serum HER‐2/neu before the start of chemotherapy was not associated with response rate, whereas elevated serum HER‐2/neu at 2 months was significantly associated with reduced long‐term clinical benefit (24weeks) (P < .001), as well as changes in HER‐2/neu levels between baseline and 2 months (P < .0001). Multivariate analysis identified a ≥20% increase of serum HER‐2/neu as an independent factor for progression‐free survival (PFS). Kinetics of serum HER‐2/neu were significantly associated with PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels of EGFR (P = .031) and after 24 weeks (P = .022). Moreover, they were significantly associated with reduced PFS (P = .016) and OS (P = .015). CONCLUSIONS. Serum HER‐2/neu and EGFR may represent useful markers for early prediction of probability of response, PFS, and OS in patients with advanced breast cancer treated with metronomic chemotherapy. Cancer 2007. © 2007 American Cancer Society.

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