Molecular profiling including epidermal growth factor receptor and p21 expression in high-risk breast cancer patients as indicators of outcome.

Abstract

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, beta-tubulin-3, multidurg resistance (MDR1), cyclooxygenase2 (COX2), and cyclin-E was measured by RT-PCR.

RESULTS:

Eighty percent of patients presented with locally advanced, or > 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.

• Authors: G Somlo, P Chu, P Frankel, W Ye, S Groshen, J H Doroshow, K Danenberg, P Danenberg
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 11 Pg. 1853-9 (Nov 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 18641005 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• ErbB Receptors
• Receptor, ErbB-2

Topics

• Adult
• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cell Growth Processes (physiology)
• Cohort Studies
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis, genetics)
• Disease-Free Survival
• ErbB Receptors (biosynthesis, genetics)
• Female
• Gene Expression
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Staging
• Receptor, ErbB-2 (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors