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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

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).

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Xu B,Guan Z,Shen Z,Tong Z,Jiang Z,Yang J,DeSilvio M,Russo M,Leigh M,Ellis C

doi

10.1186/s13058-014-0405-y

subject

Has Abstract

pub_date

2014-07-24 00:00:00

pages

405

issue

eissn

1465-5411

issn

1465-542X

pii

s13058-014-0405-y

journal_volume

pub_type

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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