Abstract
2094 Background: The aim of this prospective study was to evaluate mechanisms of resistance to trastuzumab in patients with MBC. Methods: Sixteen patients with Her2/neu overexpressing tumors (15 were 3+ by immunohistochemistry (IHC) and one 2+ by IHC and positive by FISH) were eligible. Fourteen patients underwent biopsy and two fine needle aspirations (FNA) of newly developed lesions during transtuzumab treatment. All samples were analyzed by immunohistochemistry (IHC) (Herceptest). In all patients serial measurements of serum Her-2/neu (S-HER2) were made at baseline and during trastuzumab-based treatment by enzyme-linked immunosorbent assay (ELISA by Bender MedSystems) (cutoff point:10ng/ml). Patients whose HER-2 status changed in the metastatic site consisted group A, while the rest of the patients consisted group B. Results: The metastatic lesions in 6/16 patients (37.5%) (Group A) scored 0, +1. The rest of the cases 10/16(62.5%) (Group B) retained HER-2 overexpression in the metastatic site (+3). FNA samples were classified in group B. Baseline S-HER2 levels were elevated in 5/16 patients (3 of groupA, 2 of group B). All five patients responded initially to treatment and S-HER2 levels declined under the cutoff point. After the progression of the disease S-HER2 levels of group A remained undetectable while group B developed increased levels. There was no statistically significant difference between the two groups when we compared the period of time that each group had received trastuzumab, chemotherapy, and the number of chemotherapeutic treatments. Progression -free interval tended to be shorter in group A (median PFI of group A: 9.5 months, median PFI of group B: 12 months; p=0.1). Conclusions: These data suggest that, possibly one of the mechanisms of resistance to transtuzumab is domination of a HER-2 negative clone. Further investigations with a larger number of patients are needed to confirm this hypothesis. No significant financial relationships to disclose.
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