[1043] Expression of EGFR ligands betacellulin and tenascin C are associated with molecular response following gefitinib treatment in women with primary breast cancer.

Finn RS, Dering J, Ginther C, Wilson CA, Raab G, Pawlicki M, Gerber B, Pinter T, Eiermann W, von Minckwitz G, Mackey J, Forbes J, French T, South M, Barrett I, Chang KM, Slamon DJ.. Geffen School of Medicne at UCLA, Los Angeles, CA; Frauenklink von Roten Kreuz, Munich, Germany; Maria Sklodowska-Curi Memorial Cancer Institute, Krakow, Poland; Frauenklink der LMU, Munich, Germany; Petz Aladar County Hospital, Gyor, Hungary; Frauenklink von Roten Kreuz, Munich, Germany; JW Goethe-Universitats-Frauenklinik, Frankfurt, Germany; Cross Cancer Institute, Edmonton, AB, Canada; University of Newcastle, Newcastle, Australia; AstraZeneca, Manchester, United Kingdom

Introduction: Epidermal Growth Factor Receptor (EGFR) has been implicated in the pathogenesis of breast cancer. However, EGFR inhibitors have had limited clinical success in the treatment of breast cancer. BCIRG 103 was a pre-surgical study designed to evaluate the molecular changes that occur in primary breast cancer tissue after short-term exposure to the EGFR tyrosine kinase inhibitor gefitinib (IRESSA, AstraZeneca). Here we use analysis of variance (ANOVA) to identify genes associated with a molecular response to gefitnib in this study. Methods 59 women were enrolled and 43 were evaluable for molecular changes. Frozen tissue was obtained at baseline and after exposure to gefitnib. Agilent microarrays were performed on the baseline sample to determine the molecular subtype of breast cancer (ie luminal vs non-luminal) and to identify genes associated with molecular response to gefitnib. As reported earlier (SABCC 2005), molecular response was assigned based on changes in Ki67 mRNA and cell cycle gene set mRNA when comparing the baseline sample to the post-exposure specimen. We assigned 43 patients evaluable for molecular changes to one of three groups: (1) molecular growth inhibition, 11 pts (2) molecular growth proliferation, 9 pts (3) no significant change in Ki67 or cell cycle genes, 23 pts. Results: Of the 43 patients evaluable for response, 36 were classified as luminal breast cancers and 7 as nonluminal (basal and mesenchymal). When considering all evaluable patients, regardless of subtype, tenascin C levels were higher for patients with molecular inhibition following gefitinib treatment. In addition, when considering just the luminal subset, increased expression of betacellulin was associated with gefitinib response. Both tenascin C and betacellulin are ligands for EGFR, providing biologic rationale for these results. Conclusion: Expression of the EGFR ligands betacellulin and tenascin C are associated with molecular inhibition by gefitnib in women with primary breast cancer. Further studies validating these observations and exploring their potential as markers of clinical response to gefitnib and other EGFR targeted agents in breast cancer are warranted.
IRESSA is a trademark of the AstraZeneca group of companies.

Thursday, December 14, 2006 5:00 PM

Poster Session I: Prognosis and Response Prediction: Predictive Factors I (5:00 PM-7:00 PM)