Levels of Phosphorylated AKT in Patients With Node-Positive Breast Cancer: Correlation With Disease-Free and Overall Survival

Taxanes (paclitaxel and docetaxel) have emerged as the most powerful chemotherapeutics in breast cancer over the past decades. The B-28 clinical trial from the National Surgical Adjuvant Breast and Bowel Project (NSABP) assesses the efficacy of adding paclitaxel to the doxorubicin/cyclophosphamide regimen in the treatment of patients with axillary node positive breast cancer. The primary aim of B-28 is to determine whether four cycles of paclitaxel (Taxol (Registered Trademark)) (T) following four cycles of postoperative Doxorubicin (adriamycin (Registered Trademark) (A) and cyclophosphamide (C) will more effectively prolong disease-free survival (DFS) and survival (S) than four cycles of AC alone in patients with operable breast cancer who have one or more histologically positive axillary lymph nodes. The B-28 clinical trial tissue microarray consists of specimens from 2,000 cases enrolled. The tissue microarray set is an ideal platform for evaluating predictive markers of doxorubicin and/or paclitaxel response or resistance.

Akt, a serine/threonine protein kinase regulated by the phosphatidylinositol 3-kinase (PI3K), is of importance in cell survival, tumorigenesis, and recently shown, chemoresistance. It confers survival advantage to cells by transducing signals from growth factor receptors that activate PI3K. The primary aim of this study is to evaluate whether the levels of phosphorylated AKT are associated with disease-free and overall survival in patients with node-positive breast cancer treated with AC and/or AC followed by paclitaxel.