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

Francisco J Esteva1*, Carol D Cheli2, Herbert Fritsche1, Monica Fornier3, Dennis Slamon4, Robert P Thiel5, Diana Luftner6 and Farooq Ghani2

Author Affiliations

1 The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

2 Bayer HealthCare, LLC, Diagnostics Division, Tarrytown, NY, USA

3 Memorial Sloan Kettering Cancer Center, New York, NY, USA

4 University of California, Los Angeles, Department of Medicine, Los Angeles, CA, USA

5 Thiel Statistical Consultants, Oxford, CT, USA

6 Charité Hospital, Universitätsmedizin Berlin, Berlin, Germany

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Breast Cancer Research 2005, 7:R436-R443  doi:10.1186/bcr1020

Published: 8 April 2005



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.


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.


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 (≥ 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 ≤ 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.


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.