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Open Access 01-08-2014 | Research article

Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone

Authors: Binghe Xu, Zhongzhen Guan, Zhenzhou Shen, Zhongshen Tong, Zefei Jiang, Junlan Yang, Michelle DeSilvio, Mark Russo, Meggan Leigh, Catherine Ellis

Published in: Breast Cancer Research | Issue 4/2014

Abstract

Introduction

Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations and PTEN low in patients receiving paclitaxel alone or in combination with lapatinib.

Methods

Immunohistochemistry and mutation analyses were used to evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank tests, logistic regression and Cox models were used in analyses of these biomarkers with efficacy endpoints.

Results

In the overall population, PIK3CA mutations were associated with poorer overall survival (OS) (hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction tests (P >0.05).

Conclusions

PTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit.

Trial registration

ClinicalTrials.gov NCT00281658 (registered 23 January 2006)

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Title: Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone
Authors: Binghe Xu
Zhongzhen Guan
Zhenzhou Shen
Zhongshen Tong
Zefei Jiang
Junlan Yang
Michelle DeSilvio
Mark Russo
Meggan Leigh
Catherine Ellis
Publication date: 01-08-2014
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 4/2014
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-014-0405-y

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Abstract

Introduction

Methods

Results

Conclusions

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