Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.
Academic Article
Overview
abstract
BACKGROUND: The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiological cohorts. METHODS: We followed women with invasive breast cancer from the Nurses' Health Studies with available data on tumor PTEN expression (n=4,111) and PIK3CA mutation (n=2,930). PTEN expression was evaluated by immunohistochemistry and digitally scored (0-100%). Pyrosequencing of six hotspot mutations of PIK3CA was performed. RESULTS: We found loss of PTEN expression (≤10%) occurred in 17% of cases, and PIK3CA mutations were detected in 11% of cases. After adjusting for clinical and lifestyle factors, PTEN loss was not associated with worse breast cancer-specific mortality among all samples (hazard ratio (HR) =0.85; 95% confidence intervals (CI)=0.71-1.03) or among estrogen receptor (ER)-positive tumors (HR =0.99; 95%CI=0.79-1.24). However, among ER-negative tumors, PTEN loss was associated with lower breast cancer-specific mortality (HR =0.68; 95%CI=0.48-0.95). PIK3CA mutation was not strongly associated with breast cancer-specific mortality (HR =0.89; 95%CI=0.67-1.17). Compared with tumors without PTEN loss and without PIK3CA mutation, those with alterations (n=540) were not at higher risk (HR =1.07; 95%CI=0.86-1.34). However, women with both PTEN loss and PIK3CA mutation (n=38) were at an increased risk of breast cancer-specific mortality (HR =1.65; 95%CI=0.83-3.26). CONCLUSIONS: In this large epidemiologic study, the PTEN-mortality association was more pronounced for ER-negative tumors, and the joint PTEN loss and PIK3CA mutation may be associated with worse prognosis. IMPACT: Further studies with a larger sample of ER-negative tumors are needed to replicate our findings and elucidate underlying mechanisms.
