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

Cancer. 2007 Feb 1;109(3):496-501. doi: 10.1002/cncr.22418.

Abstract

Background: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Lobular / blood
  • Carcinoma, Lobular / drug therapy
  • Cyclophosphamide / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Kinetics
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / blood*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Epirubicin
  • Cyclophosphamide
  • Receptor, ErbB-2
  • Trastuzumab
  • Fluorouracil