P5-13-11: PTEN and Tau-Protein Expression: Predictive Value of Poor Response to Trastuzumab Plus Paclitaxel in Patients with HER2−Positive Breast Cancer.

Abstract

Abstract Backgrounds: Trastuzumab-based chemotherapy has been an active treatment in patients (pts) with HER2−positive breast cancer; however, primary and secondary resistance has occurred in pts treated with trastuzumab (H) alone or in combination with chemotherapy. Material and Methods: Biomarkers were searched using tissue microarrays (TMA) in the HER2−positive breast cancer pts treated with H and paclitaxel (P) combination chemotherapy between October 2004 and August 2010. Tumor blocks of 101 pts were analyzed for VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, Tau-protein, p27 and PTEN by immunohistochemical (IHC) analysis. Eight biomarkers were assessed to investigate the correlation with the clinical outcomes, including response rate (RR), progression free survival (PFS), and overall survival (OS). Results: With a median follow-up duration of 21.7 months (range, 9.1−55.2 months), 101 pts received H+P chemotherapy in neoadjuvant setting (n=36, 35.6%) and recurrent or metastatic setting (n=65, 64.4%). Median age was 48 (range, 19–83 years), and the majority of pts (n=95, 94.1%) had good performance status. Premenopausal pts and hormone receptor-negative pts were 48 (47.5%) and 52 (51.5%), respectively. The median cycle of H+P chemotherapy was six (range, H 1–43; P 1–21). Overall RR was 68.3% (n=69) including complete response with 7 pts, and PFS and OS were significantly longer in pts responsive to H+P chemotherapy compared with non-responsive patients (PFS, p=0.001; OS, p=0.015). Although VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, p27 and PTEN status by IHC were not significantly associated with response to H+P chemotherapy, Tau-protein showed a trend of association without statistical significance (RR, 46.2% vs. 71.6%, p=0.066). Among 13 pts with high Tau protein expression, 9 pts with both high Tau-protein and low PTEN level showed statistically significant lower RR compared with other 92 pts (22.2% vs. 72.8%; p=0.002). None of the biomarkers was related to PFS and OS in pts with recurrent or metastatic disease, and to pathologic complete response in pts after H+P chemotherapy as neoadjuvant therapy. Conclusion: Our data showed that both low PTEN level and high Tauprotein expression were significantly associated with poor response to H+P chemotherapy in patients with HER2−positive breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-11.