TLE3 as a biomarker for taxane sensitivity in breast cancer

Abstract

573 Background: The addition of taxanes (T) to chemotherapeutic regimens has not demonstrated a consistent therapeutic benefit in early stage breast cancer (Ward, HTA 2007). A recent study by Hayes, et al. suggested that HER2+ breast tumors may gain increased clinical benefit from treatment with T. The toxicity associated with T therapy compels a search for additional and or refined biomarkers of response. Methods: A dataset of IHC stains in 411 patients from Clearview Cancer Center (CCI) was mined to identify biomarkers of T response (Ring, JCO 2006). TLE3 staining with a polyclonal antibody was nominated as a candidate T-response predictor. The association with T sensitivity was tested by staining with anti-TLE3 antibody on an independent triple-negative (TN) validation cohort assembled at the Roswell Park Cancer Institute (RPCI). Results: TLE3 was identified as a candidate T sensitivity marker in the CCI cohort by identifying patients with improved five-year disease-free interval (DFI) in overall cohort (n=441, p<0.004), patients treated with CMF (n=72 p<0.02), or those treated with a AC+T regimen (n=65 p<0.04) but no association of staining with outcome in untreated patients (n=203 p=0.49) or those treated with a AC without T (n=66 p=0.97). In the RPCI TN validation cohort, TLE3 staining was significantly associated with improved five-year DFI in T treated patients (n=45 p<0.02) and all patients (n=81 p<0.015) but not AC treated patients (n=17 p=0.81). These associations were independent of grade, tumor size and nodal status in both cohorts. Conclusions: TLE3 staining is associated with improved DFI in taxane-treated patients in two independent cohorts. Given that the validation cohort was triple negative, it is unlikely that TLE3 is serving as a surrogate for ER or HER2 expression. TLE3 should be studied in large clinical trial cohorts to establish its role in taxane chemotherapy selection. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Applied Genomics Applied Genomics Applied Genomics Applied Genomics