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Title: HER-2/neu status of primary breast cancer and corresponding metastatic sites in patients with advanced breast cancer treated with trastuzumab-based therapy. Author: Pectasides D, Gaglia A, Arapantoni-Dadioti P, Bobota A, Valavanis C, Kostopoulou V, Mylonakis N, Karabelis A, Pectasides M, Economopoulos T. Journal: Anticancer Res; 2006; 26(1B):647-53. PubMed ID: 16739334. Abstract: BACKGROUND: The aim of this prospective study was to investigate whether there were changes in HER-2/neu status in newly-developed metastatic lesions following treatment with trastuzumab in advanced breast cancer patients overexpressing HER-2/neu. The utility of serological assays for HER-2/neu in such patients was also studied. PATIENTS AND METHODS: Sixteen patients with HER-2/neu-overexpressing tumors (15 were 3+ by immunohistochemistry (IHC) and one 2+ by IHC and positive by the chromogenic in situ hybridization (CISH) test) were included in the study. Fourteen patients underwent biopsy and 2 patients fine-needle aspiration (FNA) of newly-developed metastatic lesions following trastuzumab treatment. All samples were assayed for HER-2 by IHC and by the CISH test. Serial serum HER-2/neu (S-HER-2) levels were measured prior to (baseline values) and during trastuzumab-based treatment by enzyme-linked immunosorbent assay (ELISA) (cut-off point: 10 ng/ml) in all patients. The patients were divided into 2 groups: those with "altered HER-2/neu status" and those with "conserved HER-2/neu status" in the metastatic region. RESULTS: Six out of the 16 (37%) ("altered HER-2/neu status") newly-developed metastatic lesions lost their HER-2/neu overexpression and scored 0 or +1 by IHC or negative on the CISH test, while in the remaining cases (10/16, 62.5%) ("conserved HER-2/neu status"), the HER-2/neu status was unchanged (+3 by IHC or a positive CISH test). Baseline S-HER-2 levels were elevated in 5 out of 16 patients (3 of "altered HER-2/neu status", 2 of "conserved HER-2/neu status"). The serum HER-2 (S-HER-2) levels declined and returned within the normal ranges in all these 5 patients as a response to trastuzumab treatment. Following the disease progression, the S-HER-2 levels of the 3 patients with "altered HER-2/neu status" remained normal, while those of 2 with "conserved HER-2/neu status" increased. There was no statistically significant difference in the number of chemotherapeutic treatments or the median time of treatment with trastuzumab or chemotherapy between the 2 groups. Time to tumor progression (TTP) was significantly shorter in the "altered HER-2/neu status" patients (median TTP for "altered HER-2/neu status": 9.5 months, and for "conserved HER-2/neu status": 12 months; p <0.001). CONCLUSION: These data suggest that, for most patients with metastatic breast cancer treated with trastuzumab, the HER-2/neu expression as measured by IHC and/or CISH in newly-developed metastatic lesions was unchanged. However, a remarkable percentage of cases lost HER-2/neu overexpression. It is not clear whether this finding implies resistance or sensitivity to trastuzumab.[Abstract] [Full Text] [Related] [New Search]