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Annals of Oncology Advance Access originally published online on September 5, 2007
Annals of Oncology 2008 19(2):315-320; doi:10.1093/annonc/mdm429
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© 2007 European Society for Medical Oncology. For Permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

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

F. Andre1,2, R. Nahta1, R. Conforti2, T. Boulet3, M. Aziz4, L. X. H. Yuan1, F. Meslin5, M. Spielmann2, G. Tomasic3, L. Pusztai1, G. N. Hortobagyi1, S. Michiels4, S. Delaloge2 and F. J. Esteva1,*

1 Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
2 Department of Medicine and Translational Research Unit UPRES EA 03535
3 Department of Biostatistics, Laboratoire d'Immunologie des tumeurs humaines, Institut Gustave Roussy, PR1 and IFR54, Villejuif, France
4 Department of Pathology, Institut Gustave Roussy, Laboratoire d'Immunologie des tumeurs humaines, Institut Gustave Roussy, PR1 and IFR54, Villejuif, France
5 Department of Institut National de la Santé et de la Recherche Médicale U753, Laboratoire d'Immunologie des tumeurs humaines, Institut Gustave Roussy, PR1 and IFR54, Villejuif, France

* Correspondence to: Dr F. J. Esteva, Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel: +1-713-792-2817; Fax: +1-713-563-0739; E-mail: festeva{at}mdanderson.org

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.

Key words: AKT, breast cancer, EGFR, HER2

Received for publication June 19, 2007. Revision received July 19, 2007. Accepted for publication July 23, 2007.


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