Kinetics of serum HER‐2/neu changes in patients with HER‐2‐positive primary breast cancer after initiation of primary chemotherapy

AbstractBACKGROUND.The purpose of the study was to determine the utility of quantitation of the extracellular domain (ECD) of the HER‐2/neu receptor in the serum for predicting response to treatment in patients with primary breast cancer receiving neoadjuvant therapy.METHODS.HER‐2/neu ECD was measured in sera obtained from 39 patients with HER‐2‐amplified stage II‐III primary breast cancer undergoing neoadjuvant chemotherapy. Patients were randomly assigned to either 4 cycles of paclitaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (n = 10) or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks (n = 29). Changes in HER‐2 ECD were monitored with the Bayer HER‐2/neu assay over 6 months and correlated with pathological response to treatment.RESULTS.Before initiation of chemotherapy, 28.2% of patients had elevated concentration of the HER‐2 ECD (>15 ng/mL). The median baseline serum HER‐2 ECD concentration was 13.6 ng/mL (mean ± SD, 20.3 ± 35.5 ng/mL). A decrease in the median HER‐2 ECD levels from baseline to Week 3 and from baseline to Week 6 of chemotherapy was seen regardless of treatment regimen. No significant difference in baseline HER‐2 ECD levels was observed between the groups who achieved pathological complete response (pCR) and the group with residual disease (P = .41). However, a 9% drop from Week 3 to Week 6 after initial chemotherapy was predictive of pCR (P = .04).CONCLUSION.A decrease in serum HER‐2 ECD levels early during treatment was associated with pathological response in patients receiving primary chemotherapy, particularly trastuzumab‐based regimens. Serum HER‐2 ECD levels may serve to monitor neoadjuvant therapy in HER‐2‐positive primary breast cancer. Cancer 2007;109:487–495. © 2006 American Cancer Society.