Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies

Breast Cancer Res. 2005;7(4):R436-43. doi: 10.1186/bcr1020. Epub 2005 Apr 8.

Abstract

Introduction: The purpose of this retrospective study was to determine the clinical utility of serum HER2/neu in monitoring metastatic breast cancer patients undergoing trastuzumab-based therapy and to compare these results with those obtained using cancer antigen (CA) 15-3. We also sought to determine whether early changes in serum HER2/neu concentrations could be a predictor of progression-free survival.

Methods: Sera were obtained retrospectively from 103 women at four medical institutions. Patients eligible for participation were women with metastatic breast cancer who had HER2/neu tissue overexpression and were scheduled to be treated with trastuzumab with or without additional therapies as per the established practices of the treating physicians. A baseline serum sample for each patient was taken before trastuzumab-based therapy was started. Patients were subsequently monitored over 12 to 20 months and serum samples were taken at the time of clinical assessment and tested with Bayer's HER2/neu and CA15-3 assays.

Results: Concordance between clinical status in patients undergoing trastuzumab-based treatment and HER2/neu and CA15-3 used as single tests was 0.793 and 0.627, respectively, and increased to 0.829 when the tests were used in combination. Progression-free survival times did not differ significantly in patients with elevated baseline HER2/neu concentrations (> or = 15 ng/mL) and those with normal concentrations (<15 ng/mL). However, progression-free survival differed significantly (P = 0.043) according to whether the patient's HER2/neu concentration at 2 to 4 weeks after the start of therapy was >77% or < or = 77% of her baseline concentration. The median progression-free survival times for these two groups were 217 and 587 days, respectively. A similar trend was observed for a subcohort of patients treated specifically with a combination of trastuzumab and taxane.

Conclusion: These findings indicate that serum HER2/neu testing is clinically valuable in monitoring metastatic breast cancer patients undergoing trastuzumab-based treatment and provides additional value over the commonly used CA15-3 test. The percentage of baseline HER2/neu concentrations in the early weeks after the start of therapy may be an early predictor of progression-free-survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Metastasis
  • Predictive Value of Tests
  • Receptor, ErbB-2 / blood*
  • Retrospective Studies
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • Trastuzumab