Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer

• Published in: Annals of oncology Vol. 19; no. 2; pp. 315 - 320
• Main Authors: Andre, F., Nahta, R., Conforti, R., Boulet, T., Aziz, M., Yuan, L. X. H., Meslin, F., Spielmann, M., Tomasic, G., Pusztai, L., Hortobagyi, G. N., Michiels, S., Delaloge, S., Esteva, F. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Age Factors; Aged; AKT; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - analysis; Breast cancer; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Chi-Square Distribution; Cohort Studies; Combined Modality Therapy; Disease-Free Survival; EGFR; ErbB Receptors - genetics; ErbB Receptors - metabolism; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; HER2; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Predictive Value of Tests; Probability; Proportional Hazards Models; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Randomized Controlled Trials as Topic; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Risk Assessment; Survival Analysis; Time Factors; Treatment Outcome; Tumors; breast cancer; AKT; EGFR, HER2; Phosphorylation; Akt protein kinase; erbB2 Gene; Early stage; Breast cancer; Malignant tumor; Gene expression; Epidermal growth factor receptor; Human Epidermal growth factor Receptor 2; EGFR; Mammary gland diseases; C-Onc gene; Predictive value; HER2; Protooncogene; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdm429

Background: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues. Patients and methods: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction. Results: pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2− tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2−/EGFR+ and HER2−/EGFR− tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70). Conclusions: AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.