Prognostic value of expression of intracellular and extracellular domains of HER2 in patients with HER2-possitive breast cancer

Background: HER2 consists of an extra cellular domain (the target for trastuzum ab), a transmembrane domain, and an in tracellular domain, which is recognized by an antibody used in the immunohisto chemical assessment of HER2 overex pression. The study consisted of 31 pa tients with metastatic breast cancer treated with trastuzumab. The aim of the studywas to evaluate ret rospectively expression of extracellular and intracellular HER2 domains in primary breast cancers treated with surgery and to assess their correlation with biological features of tumours, disease-free survival, overall survival, as well as pro gression-free survival and survival since the start of trastuzumab treatment. Material and methods: All these patients relapsed and were treated with tras tuzumab because of metastatic disease ‐ none of them received trastuzumab in an adjuvant setting. Two kinds of anti bodies were used in immunohisto chemical evaluation: against extracellu lar and intracellular domains of the HER2. Results: A significant correlation be tween different patterns of HER2 domain overexpression and disease-free sur vival was found. Disease-free survival (the time from the primary operation to re lapse ‐ prior to the start of any palliative treatment) was the shortest in patients with overexpression of both domains compared to patients without overex pression of both domains and the group with intracellular domain overexpression combined with absence of extracellular domain overexpression (median 13.2 vs. 24.3 vs. 52.4 months, p= 0.01). There was no significant difference between these 3 groups of patients in aspects of bio logical features of tumours, overall sur vival, progression-free survival and survival since the start of trastuzumab treatment. Conclusion: Concurrent assessment of ex tracellular and intracellular domains of HER2 may have prognostic value for HER2-positive patients.