Publication Date:
2014-07-26
Description:
IntroductionPhosphatidylinositol 3-kinase (PI3K) pathway deregulation (i.e. 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? ?0.05). Conclusion: 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 registrationClinicalTrials.gov NCT00281658 (registered 23 January 2006)
Print ISSN:
1465-5411
Electronic ISSN:
1465-542X
Topics:
Medicine
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