Research article

TLE3 as a candidate biomarker of response to taxane therapy

Swati A Kulkarni¹ , David G Hicks² , Nancy L Watroba¹ , Christine Murekeyisoni¹ , Helena Hwang³ , Thaer Khoury³ , Rodney A Beck⁴ , Brian Z Ring⁵ , Noel C Estopinal⁶ , Marshall T Schreeder⁷ , Robert S Seitz⁴ and Douglas T Ross⁵

¹  Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA

²  Department of Pathology and Laboratory Medicine, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA

³  Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA

⁴  Applied Genomics Inc., 601 Genome Way, Huntsville, AL 35806, USA

⁵  Applied Genomics Inc., 863 Mitten Road #103, Burlingame, CA 94010, USA

⁶  Department of Radiation Oncology, Center for Cancer Care, Suite 10, 201 Sivley Road SW, Huntsville, AL 35805, USA

⁷  Department of Medical Oncology, Clearview Cancer Institute, 3601 CCI Drive, Huntsville, AL 35805, USA

author email corresponding author email

Breast Cancer Research 2009, 11:R17doi:10.1186/bcr2241

Published:	23 March 2009

Abstract

Introduction

The addition of taxanes (Ts) to chemotherapeutic regimens has not demonstrated a consistent benefit in early-stage breast cancer. To date, no clinically relevant biomarkers that predict T response have been identified.

Methods

A dataset of immunohistochemistry stains in 411 patients was mined to identify potential markers of response. TLE3 emerged as a candidate marker for T response. To test the association with T sensitivity, an independent 'triple-negative' (TN) validation cohort was stained with anti-TLE3 antibody.

Results

TLE3 staining was associated with improved 5-year disease-free interval (DFI) in the overall cohort (n = 441, P < 0.004), in patients treated with cyclophosphamide (C), methotrexate, and 5-fluorouracil (n = 72, P < 0.02), and in those treated with regimens containing doxorubicin (A) and a T (n = 65, P < 0.04). However, no association was shown with outcome in untreated patients (n = 203, P = 0.49) or those treated with a regimen containing A only (n = 66, P = 0.97). In the TN cohort, TLE3 staining was significantly associated with improved 5-year DFI in all patients (n = 81, P < 0.015), in patients treated with AC + T (n = 45, P < 0.02), but not in patients treated with AC (n = 17, P = 0.81). TLE3 was independent of tumor size, nodal status, and grade by bivariable analysis in both cohorts.

Conclusions

TLE3 staining is associated with improved DFI in T-treated patients in two independent cohorts. Since the validation study was performed in a TN cohort, TLE3 is not serving as a surrogate for estrogen receptor or HER2 expression. TLE3 should be studied in large clinical trial cohorts to establish its role in T chemotherapy selection.