The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse

Abstract

Overexpression of the HER2-receptor in early breast cancer (EBC) patients is associated with aggressive tumor behavior. However, women suffering from HER2-positive EBC benefit from trastuzumab treatment. As the HER2 status of the primary tumor may differ from that of disseminated tumor cells (DTC) in bone marrow (BM), the aim of this study was (1) to compare the HER2 status of the primary tumor (prim-HER2-status) with that of DTC (DTC-HER2-status) and (2) to analyze the influence of the DTC-HER2-status on patient survival. For this purpose, BM aspirates from 569 EBC patients were analyzed for the presence of DTC. The DTC-HER2-status was identified by a double-staining procedure against cytokeratin and the HER2-receptor. DTC were detected in 151 (27%) patients. The concordance between the HER2 status of DTC and the primary tumor was 51%. In patients with detectable DTC, mean disease-free survival was 77.44 (95% CI 74.72-80.17) months for DTC-HER2-negative and 55.15 (95% CI 48.57-61.79) months for DTC-HER2-positive patients (p=0.044). The multivariate analysis showed that the DTC-HER2-status was an independent predictor of disease-free survival. In conclusion, the presence of HER2-positive DTC in EBC patients is associated with an increased risk of relapse. Due to the low concordance between the HER2 status of the primary tumor and DTC, only a minority (13%) of the DTC-HER2-positive patients was treated with trastuzumab. These patients might, however, benefit from HER2-directed therapy.