Annals of Oncology Advance Access published online on July 17, 2008
Annals of Oncology, doi:10.1093/annonc/mdn402
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Molecular profiling including epidermal growth factor receptor and p21 expression in high-risk breast cancer patients as indicators of outcome
1 Department of Medical Oncology and Therapeutics Research
2 Department of Anatomic Pathology, City of Hope National Medical Center, Duarte, CA
3 Department of Biochemistry, Keck School of Medicine, University of Southern California, Los Angeles, CA
4 Department of Biostatistics, City of Hope National Medical Center, Duarte, CA
5 Department of Biostatistics, Keck School of Medicine, University of Southern California, Los Angeles, CA
6 Response Genetics, Inc., Los Angeles, CA, USA
* Correspondence to: Dr G. Somlo, Department of Medical Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA. Tel: +1 626 359-8111 ext. 62867; Fax: +1 626 301-8898; E-mail: gsomlo{at}coh.org.
Background: Patients with high-risk primary breast cancer remain at high risk for relapse. More precise prognostic and predictive tools are needed to improve treatment of such patients.
Patients and methods: Formalin-fixed, paraffin-embedded tumors from 239 high-risk breast cancer patients were examined for expression of human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), estrogen receptor, progesterone receptor, Ki-67, p16, p21, p27, and p53 by immunohistochemistry. Gene expression of EGFR, HER2, glutathione S-transferase-Pi (GSTP1), excision repair cross complementation1 (ERCC1), p21, β-tubulin-3, multidurg resistance (MDR-1), cyclooxygenase2 (COX-2), and cyclin-E was measured by RT-PCR.
Results: Eighty percent of patients presented with locally advanced, or 
10 axillary nodal metastasis, and 20% with inflammatory breast cancer. The median age was 46 years (26–62 years) and the median number of involved axillary lymph nodes was 12 (0–42). At a median follow-up of 86 months, relapse-free survival (RFS) and overall survival for the entire group were 50% (95% CI 43% to 57%) and 62% (95% CI 56% to 69%). Multivariate Cox stepwise analysis resulted in a simple model for RFS consisting only of p21 expression, EGFR expression assessed by RT-PCR, and number of axillary nodal metastases.
Conclusion: A prognostic model on the basis of the expression of a limited number of proteins and genes may help to guide target-specific therapies in patients with high-risk breast cancer.
epidermal growth factor receptor, high-risk breast cancer, prognosis, p21
Received for publication May 8, 2008. Accepted for publication May 26, 2008.