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TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial
J M S Bartlett1, T O Nielsen2, D Gao2
1Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
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.
Insights
TLE3 expression was investigated as a predictor of taxane benefit in breast cancer patients. The study found TLE3 is not a viable biomarker for predicting taxane benefit.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- TLE3, a nuclear transcriptional repressor, is downstream of WNT signaling pathways.
- TLE3 has been hypothesized to predict benefit from adjuvant taxane chemotherapy.
Purpose of the Study:
- To evaluate TLE3 expression as a predictive biomarker for taxane benefit in breast cancer patients.
- To assess the association between TLE3 expression levels and relapse-free survival in the MA.21 trial.
Main Methods:
- Tissue microarrays from 1097 breast cancer patients in the MA.21 trial were analyzed for TLE3 expression using immunohistochemistry.
- Both visual and automated scoring methods were employed to quantify TLE3 positivity.
- The predictive effect of TLE3 on relapse-free survival was tested using a pre-specified cut-point of 30% positive cells.
Main Results:
- A higher proportion of MA.21 tumors (83.2% visual, 80.6% automated) were TLE3 positive compared to previous observations (58.6%).
- TLE3 expression was significantly associated with estrogen receptor (ER) expression (91.2% of ER-positive tumors were TLE3+).
- No predictive effect of TLE3 expression on taxane benefit was observed at the median 8-year follow-up, using established or exploratory cut-points.
Conclusions:
- The pre-specified TLE3 positivity cut-point of 30% did not predict taxane benefit in the MA.21 cohort.
- TLE3 expression is not a viable biomarker for predicting taxane benefit in breast cancer patients.
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