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Annals of Oncology Advance Access originally published online on November 15, 2007
Annals of Oncology 2008 19(4):669-674; doi:10.1093/annonc/mdm522
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© The Author 2007. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer

Y. Eralp1,*, D. Derin1, Y. Ozluk2, E. Yavuz2, N. Guney1, P. Saip1, M. Muslumanoglu3, A. Igci3, S. Kücücük4, M. Dincer4, A. Aydiner1 and E. Topuz1

1 Department of Medical Oncology, Institute of Oncology
2 Department of Pathology, Istanbul Medical Faculty
3 Department of General Surgery, Istanbul Medical Faculty
4 Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey

* Correspondence to: Dr Y. Eralp, Department of Medical Oncology, Institute of Oncology, Istanbul University, Topkapi, 34390 Istanbul, Turkey. Tel: +90-212-4142434; Fax: +90-212-5348078; E-mail: yeralp{at}yahoo.com

Background: Triple-negative breast cancer is estimated to account for 15%–20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer.

Patients and methods: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated.

Results: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03).

Conclusion: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

Key words: chemoresistance, EGFR, MAPK, prognosis, triple-negative breast cancer

Received for publication July 23, 2007. Revision received October 7, 2007. Accepted for publication October 9, 2007.


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