Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1-/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1- phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.
Keywords: Akt1; Biomarkers; Breast cancer; Chemotherapy; E2F1; Immunohistochemistry; Phosphorylation.