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

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.

Figure 1

ROC curve analysis for progression of metastatic breast cancer in 26 patients. Nineteen of these patients were treated with trastuzumab (Herceptin) in combination with a taxane, one with trastuzumab (Herceptin) in combination with vinorelbine, and six with single-agent Herceptin without chemotherapy. The curve shows disease progression as a function of the percentage of change in the HER2/neu concentration from baseline to 2 to 4 weeks after the start of therapy. HER, human-epidermal-growth-factor receptor; ROC, receiver operating characteristic.

Figure 2

Kaplan–Meier curves for progression-free survival in patients with metastatic breast cancer given trastuzumab-based treatment. Curves were plotted for two groups of patients, those whose HER2/neu concentrations seen at 2 to 4 weeks of trastuzumab-based therapy were ≤ 77% of the baseline concentrations and those for whom it was >77% (median progression-free survival time 587 and 217 days, respectively) df = 1. HER, human-epidermal-growth-factor receptor.

Figure 3

Kaplan–Meier curves for progression-free survival in patients with metastatic breast cancer receiving trastuzumab–taxane. Differences between the survival times (days) for patients whose HER2/neu concentrations at 2 to 2 weeks of treatment had fallen to ≤ 77% of baseline values and those whose values had remained at >77% of baseline values (respective survival times 587 and 119 days).