Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer

Abstract

Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS.

p-mTOR expression is associated with better prognosis in luminal breast carcinoma

“…Moreover, in the same study, 62.8% of grade 1 carcinomas express p-mTOR (vs 31.9% of grade 2 and 23.4% of grade 3) 7. Furthermore, it was recently demonstrated in patients with locoregional relapse that p-mTOR expression is associated with decreased risk of early relapse, and that high levels of p70S6K (a downstream target of mTORC1), are associated with prolonged OS in lymph node-positive patients 21 22. Others have demonstrated that p-mTOR-expression is more frequent in invasive BCs as compared to carcinoma in situ, or normal breast epithelium,23 yet, based on these results, one cannot assume that the percentage of p-mTOR-expressing tumours will be higher in advanced disease compared to localised invasive disease, or that higher mTOR expression is a surrogate for mTOR pathway activation.…”

“…This was a retrospective, observational, single-centre-based study, which may limit the generalisability of our findings. We report p-mTOR expression association with outcome after controlling for some of the determinants of BC treatment (age, grade, size, lymph node status, hormone receptor status and HER2 status); however, we were incapable of determining if it was prognostic or predictive, since we were unable to study the possible recently suggested interaction between p-mTOR expression and chemotherapy 21. Note, that because p-mTOR expression was associated with smaller and lower-grade tumours, it was more likely to be detected in patients who had not undergone adjuvant chemotherapy; thus, even if data on adjuvant chemotherapy were available, it would be reasonable to expect a greater magnitude of the effect on outcome of p-mTOR expression.…”

P-mTOR Expression and Implication in Breast Carcinoma: A Systematic Review and Meta-Analysis

“…In the summary analysis, multivariate data were extracted when the results involved multivariate and univariate analyses, taking confounding factors into account. Eight studies provided integrated original information of the relationship between p-mTOR expression and clinical pathological parameters in breast carcinoma directly [22–25, 27–29]. One article assessed the prognostic value of p-mTOR (DFS) in breast carcinoma by the Kaplan-Meier method [26].…”

Phosphatidylinositol 3-kinase/Akt signaling as a key mediator of tumor cell responsiveness to radiation

“…Immunohistochemical analysis of phosphorylated Akt1 at S473 implied that activated Akt1 was a potential predictive biomarker for radiotherapy responsiveness, in patients with head and neck cancer and cervical cancer [37,38]. Activated Akt was also reported as a predictive marker for disease-free survival and overall survival in breast cancer patients following hormone therapy [121], and for responsiveness to chemotherapy with tamoxifen [122].…”