Epidermal growth factor receptor (EGFR) mutations in breast and cervical cancer

Abstract

20101 Background: EGFR is a tyrosine kinase receptor in the HER family which is widely expressed in a number of epithelial tumors and is believed to play a key role in cell proliferation. Molecular analysis of the EGFR gene in patients with non-small-cell lung cancer have identified a distinct subset of tumors that possess specific point mutations in the tyrosine kinase region of the EGFR gene, which correlate to response to tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. Clinical trials involving TKIs are currently under way for patients with breast and cervical cancer. While responses thus far may have been modest it is unclear whether specific EGFR mutations are present in breast and cervical cancers which identify patients with improved prognosis and better response to therapy in these cancers. Using clinical samples with 5 years of follow-up clinical data, we have set out to determine whether EGFR mutations exist in breast and cervical cancers, and how these mutations, if any, correlate with the clinical data. Methods: We plan to perform sequence analysis of the tyrosine kinase domain of the EGFR gene (exons 18–24) in 50 archival breast and 44 cervical cancer specimens using PCR amplification and sequencing of genomic DNA. Clinical information has been extracted from patient charts on samples and will be correlated with the presence of any EGFR mutations identified. Results: To date we have collected 50 breast and 44 cervical tumor blocks and have isolated genomic DNA from the specimens. Sequencing for point mutations in exons 18–24 is underway. Clinical data on the cervical cancer specimens revealed a mean age at diagnosis of 48.2 years, tumor grades that were mostly intermediate (50%) and high (45%), and all FICO stages at diagnosis (43% stage I, 30% stage II, 5% stage III, 5% stage IV). In addition the rate of recurrence was 32%, and survival rate was 82% with an average time of follow-up for the set of 4.9 years. Conclusions: Our data will further elucidate the role of point mutations in EGFR gene in breast and cervical cancer prognosis and response to therapy, and will complement data currently being collected in clinical trials using TKIs. No significant financial relationships to disclose.