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Annals of Oncology Advance Access originally published online on September 14, 2007
Annals of Oncology 2007 18(11):1793-1798; doi:10.1093/annonc/mdm406
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© 2007 European Society for Medical Oncology

breast cancer

Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer

F. Meslin1,{dagger}, R. Conforti2,{dagger}, C. Mazouni3, N. Morel5, G. Tomasic2, F. Drusch2, M. Yacoub1, J. C. Sabourin2, J. Grassi5, S. Delaloge2, M. C. Mathieu2, S. Chouaib1, F. Andre2,{ddagger} and M. Mehrpour1,4,{ddagger},*

1 Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Immunologie des Tumeurs Humaines: Interaction effecteurs cytotoxiques-système tumoral, Institut Gustave Roussy PR1 and IFR 54, 94805 Villejuif
2 Breast cancer unit and translational research unit UPRES03535, Institut Gustave Roussy, Villejuif
3 Service d'anatomopathologie, Hopital La Timone, Marseille, France
4 Chinese Academy of Sciences, Laboratory of Apoptosis and Cancer Biology, The National Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing, China
5 CEA Saclay Service de Pharmacologie et d'Immunologie Bâtiment 136 91191 Gif sur Yvette cedex, France

* Correspondence to: Dr M. Mehrpour, Institut National de la Santé et de la Recherche Médicale, U 753, Laboratoire d'Immunologie des Tumeurs Humaines: Interaction effecteurs cytotoxiques-système tumoral, Institut Gustave Roussy, PR1, F-94805 Villejuif Cedex, France. Tel: +33-142114650; Fax: +33-1-42115288; E-mail: mehrpour{at}ioz.ac.cn

Background: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer.

Patients and methods: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors.

Results: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45–2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2–0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors.

Conclusion: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.

Key words: breast cancer, cellular prion protein, chemotherapy, clinical drug resistance, estrogen receptor negative

{dagger} Both authors equally contributed to this work.

{ddagger} Both authors equally contributed to this work as senior authors.

Received for publication January 2, 2007. Revision received July 3, 2007. Accepted for publication July 4, 2007.


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