Serum CD44 levels and overall survival in patients with HER2-positive breast cancer

CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival in patients with breast cancer. We retrospectively identified 110 patients with breast cancer who had been treated at The University of Texas MD Anderson Cancer Center (MDACC) from September 2001 to May 2004. Sera were collected before definitive surgery in patients with stage I or II breast cancer, before initiation of neoadjuvant chemotherapy (if indicated) for patients with stage I-III breast cancer, and before initiation of systemic therapy in patients with stage IV breast cancer. sCD44 levels were determined using an enzyme-linked immunosorbent assay. The median age at diagnosis was 51 years (range, 28.6-87.1 years). sCD44 concentration was correlated with tumor stage (P = 0.0308). sCD44 serum concentration did not predict pathological response in patients treated with neoadjuvant chemotherapy. Among patients with distant metastases, sCD44 levels were significantly higher in patients with liver involvement than in patients with metastases at other sites. The overall survival rate did not differ between patients with high sCD44 concentration and patients with low sCD44 concentration. However, sCD44 concentration was a significant predictor of overall survival for patients with HER2-positive breast cancer, while no difference in overall survival rates was observed in patients with HER2-negative breast cancer. To the best of our knowledge, this is the first study to show an association between circulating sCD44 levels and survival in HER2-positive breast cancer patients. Our results suggest a role for sCD44 as a prognostic marker. Furthermore, sCD44 level may offer a new clinical therapeutic target in HER2-positive breast cancer.