Breast cancer is the most commonly occurring
malignancy and the leading cause of
cancer-related death in women.
Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant
metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in
cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN
tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR
proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of
metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/
mTOR protein expression may be more useful in predicting TNBC
clinical course than the analysis of single
protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.