PTEN loss is a predictive marker for HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

Purpose: The purpose of this study was to retrospectively investigate the response to trastuzumab in breast cancer patients in terms of the potential roles of several oncogenic pathways (phosphatase and tensin homolog (PTEN) and phosphatidylinositol 3-kinase (PI3K)) in relation to HER2 status. Methods: Paraffin-embedded primary tumor tissues of 100 HER2 positive metastatic breast cancer patients who received trastuzumab were analyzed with immunohistochemistry for p85 (PI3K) and PTEN. The relationship between variables was tested via chi-square, Fischer's exact test and Mann-Whitney U test, where appropriate. Progression-free survival (PFS) and overall survival (OS) were calculated with the Kaplan-Meier method and survival curves of subgroups were compared with the log-rank test. Results: The level of immunohistochemical expression of PI3K was 42%. Loss of PTEN was observed in 43% of the patients. PTEN-expressing tumors had statistically higher response rates for trastuzumab than tumors not-expressing PTEN (p=0.012). PI3K expression had no significant effect on trastuzumab response. Median PFS for PTEN-expressing and not-expressing tumors were 15.3 months (95% CI, 12.634) and 12.1 months (95% CI, 7.9-16.2), respectively (p=0.04). The level of PI3K expression had no effect on PFS and OS in our patient population. Conclusions: Loss of PTEN predicted poorer response to trastuzumab treatment and shorter PFS but not OS. We could not find an effect of PI3K expression on the above-mentioned parameters.