[1004] Reassessment of HER2 status in HER2 negative or HER2 unknown breast cancer patients with recurrent metastatic disease by analyzing serum HER2 and HER2 status of circulating tumor cells.
Fehm T, Lane N, Solomayer E, Wallwiener D, Uhr J.. University Tuebingen, Tuebingen, Germany; UT Southwestern, Dallas, TX
Introduction:
Several studies have indicated that HER2 status of HER2 negative patients can change during course of disease. Therefore, the HER2 status should be reassessed at the time of disease progression to optimize treatment decisions. Since metastatic tissue may not be available, serum HER2 status can be analyzed. A second method is the evaluation of HER2 status in circulating tumor cells (CTCs). Therefore, the aim of this study was to determine the serum HER2 status of serum and corresponding CTCs in patients initially HER2 negative or of unknown HER2 status with metastatic disease.
Methods: Blood samples were obtained from 77 metastatic breast cancer patients with negative (n=47) or unknown (n=30) HER2 status. Serum HER2 was determined using the commercial HER-2/neu ELISA-kit (Oncogene Science, MA, USA). 15 ng/ml was used as cut-off. CTCs were detected by a slide based assay using ferrofluid/immunomagnetic enrichment and characterized by pheno- and genotyping. Alternatively, a commercial kit (Adnagen, Langenhagen, Germany) based on RT-PCR was used for CTC detection and characterization.
Results:
77 metastatic breast cancer patients were included in the analysis. 19 of 77 (25%) metastatic patients had elevated serum HER2 levels. CTCs could be detected in 20 of 67 patients. 8 of these (40%) patients had CTCs with HER2 amplification. There was concordance between HER2 status of CTCs and serum HER2 in 15 of 20 patients (75%) (Table 1). In 5 patients non concordant results were obtained. Three patients with elevated serum HER2 levels had HER2 negative CTCs whereas 2 patients with HER2 amplified CTCs had normal serum HER2 levels.
Conclusions:
Our study confirms that a subset of HER2 negative patients develop elevated serum HER2 levels and HER2 positive CTCs associated with metastatic disease. However, nonconcordant results were obtained in 25% of patients using both methods. Similar nonconcordance occurs in primary breast carcinomas. Therefore, we hypothesize that different mechanisms may account for shedding HER2 versus its expression. Hence, correlating clinical responses to Herceptin based on each method should be further studied to help determine when such treatment should be given.
HER2  status N=77 | Serum HER2 negative n=58 | Serum HER2 positive n=19 | Total |
| CTC HER2 negative | 9 | 3 | 12 |
| CTC HER2 positive | 2 | 6 | 8 |
| CTC not detected | 47 | 10 | 57 |
Thursday, December 14, 2006 5:00 PM
Poster Session I: Detection and Diagnosis: Circulating Markers (5:00 PM-7:00 PM)