HER2 expression in disseminated tumor cells (DTC) and corresponding primary tumors of breast cancer patients

Abstract

9580 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with poor prognosis. Several studies have indicated that these patients may benefit from secondary adjuvant immunotherapy. HER2 protein is suggested as one of the promising targets. The phenotype of the primary tumor is the current gold standard to make antibody based treatment decisions. However, the antigenic profile of primary tumors and DTC may be different. The aims of this study were (1) to determine the HER2 status of DTC in BM of breast cancer patients (2) and to compare the HER2 status of DTC and corresponding primary tumors. Method: Cytospins from bone marrow aspirates of 124 primary breast cancer patients (stage I-III) were analyzed for this study. A double labeling procedure was used for the identification of cytokeratin-positive (CK+)/HER2 positive cells. Slides were incubated with the pan-anti-cytokeratin antibody C11 conjugated to FITC and the polyclonal rabbit antibody CB11 against the HER2 protein. CB11 was detected by a secondary antibody labeled with Texas Red. HER2 status of the primary tumor was immunohistochemically assessed by the HERCEP-test (Dako Co., CA). Results: Disseminated tumor cells (DTC) were detected in the bone marrow of 47 patients. The number of DTC ranged from 1 to 70 per slide. 24 of these patients had HER2 positive DTC. HER2 positivity (score: 2+/3+) could be demonstrated in 12 of 46 primary tumors. Concordance rate between primary tumor and DTC was 63%. In three patients with HER2 positive tumors HER2 negative DTC were detected. In contrast, 14 patients with HER2 negative tumors (score: 0/1+) had HER2 positive DTC. The HER2 expression in DTC was heterogeneous in 8 of 20 patients with more than one CK-positive cell. Conclusions: (1) HER2 positive DTC can be detected in patients with HER2 negative primary tumors. Therefore, the antigenic profile of DTC should be included in the treatment decision for antibody based strategies. (2) The DTC are heterogeneous with regard to HER2 positivity. The effect of heterogeneity on the patient’s response is yet to be determined. No significant financial relationships to disclose.