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TLE3 as a
biomarker for taxane sensitivity
in breast cancer.
Poster
at American
Society of Clinical Oncology (ASCO) 2008
Swati
A Kulkarni1, David
G Hicks2, Nancy
Watroba1, Christine
Murekeyisoni1, Rodney
A Beck3, Brian
Z Ring3, Noel
Estopinal3, Marshall
Schreeder5, Robert
S Seitz3, and Douglas
T Ross3
1Surgical
Onoclogy, Roswell Park
Cancer Institute (Buffalo,
NY),
2Pathology and Laboratory
Medicine, University
of Rochester
(Rochester,
NY),
3Applied Genomics, Inc (Huntsville, AL), 4Radiation
Oncology, Center for Cancer Care (Huntsville,
AL),
5Medical Oncology, Clearview
Cancer
Institute (Huntsville,
AL).
Abstract
Background:
The addition
of taxanes (T) to chemotherapeutic regimens has not
demonstrated a consistent therapeutic benefit in early stage breast
cancer
(1). A
recent study by Hayes, et al. suggested that HER-2+ breast tumors may
gain increased
clinical benefit from treatment with T (2). 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 Institute
(CCI)
was mined to identify biomarkers of T response (3). 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 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 clear that TLE3 is not serving as a surrogate for ER or HER-2
expression.
TLE3 should be studied in large clinical trial cohorts to establish its
role.
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