Predictive and Prognostic Significance of p27, Akt, PTEN and PI3K Expression in HER2-Positive Metastatic Breast Cancer

Abstract

<b>Background:</b> The phosphatidylinositol 3’-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2-overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosisand resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognosticsignificance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway,in HER2-positive metastatic breast cancer (MBC), retrospectively. Materials and <br/><b>Methods</b>: Fifty-four HER2-positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group.All of the patient’s breast tissue samples were examined for p27 and Akt expression. In addition, twenty-fivepatients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt,PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographicfeatures, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed.<br/><b>Results</b>: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively.Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend towardstatistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there wasno significant relationship between the other immunohistochemical variables and OS. When we analyzed groupsregarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective responserate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negativegroups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and25.6 months vs 52.0 months, p=0.007, respectively). <br/><b>Conclusions</b>: p27, Akt, PTEN and PI3K expression is notstatistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluationof p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis inHER2-positive MBC.