TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial.
BACKGROUND
TLE3, a nuclear transcriptional repressor downstream of WNT signalling pathways, has been hypothesised as predictive of benefit from adjuvant taxane.


METHODS
MA.21 tissue microarrays were constructed from 1097 out of 2104 (52%) patients. TLE3 staining by immunohistochemistry used validated methodology. Continuous TLE3+ (percentage of cells staining positive) was assessed with both visual and automated scoring. The primary objective was to test the predictive effect of TLE3 on relapse-free survival using the MA.21 EC/T and CEF arms and the previously defined cut-point of 30% of cells staining positive in ⩾1 core/tumour.


RESULTS
MA.21 patients had 83.2% TLE3 positive (TLE3+) tumours by visual score and 80.6% TLE3+ by automated image analysis while the previously observed rate of TLE3+ cases was 58.6%. TLE3 expression was significantly associated with ER expression (91.2% of ER-positive tumours were TLE3+; P<0.0001). At median 8-year follow-up, there was no evidence of a predictive effect of TLE3 expression with respect to taxane benefit using the established 30% or exploratory quartile cut-points.


CONCLUSIONS
Proportionately more MA.21 patient tumours than expected were TLE3+. The pre-specified TLE3+ cut-point of 30% was not predictive of taxane benefit. TLE3 expression does not represent a viable biomarker for taxane benefit in breast cancer.
Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
J M S
JM
Bartlett
Genetic Pathology Evaluation Centre, British Columbia (BC) Cancer Agency, Vancouver, British Columbia V5Z 1M9, Canada.
T O
TO
Nielsen
Genetic Pathology Evaluation Centre, British Columbia (BC) Cancer Agency, Vancouver, British Columbia V5Z 1M9, Canada.
D
D
Gao
BC Cancer Agency, University of British Columbia, Vancouver, British Columbia V5Z 4E6, Canada.
K A
KA
Gelmon
Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
M A
MA
Quintayo
Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
J
J
Starczynski
NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada.
L
L
Han
Saint John Regional Hospital, Saint John, New Brunswick E2L 4L4, Canada.
M J
MJ
Burnell
Juravinski Cancer Clinic, Hamilton Health Sciences, McMaster University, Hamilton, Ontario L8V 5C2, Canada.
M N
MN
Levine
NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada.
B E
BE
Chen
NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada.
L E
LE
Shepherd
NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada.|NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada.
J W
JW
Chapman
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D056970:Co-Repressor Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000517:prevention & control; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D056970:Co-Repressor Proteins; C570667:TLE3 protein, human; D043823:Taxoids; C080625:taxane