Limits...
TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Visually assessed TLE3 staining and outcome by treatment arm. (A) Recurrence-free survival by Visual TLE3: Status stratified by allocation to EC/T or CEF: TLE− CEF=patients with <30% TLE3 tumour-positive cells allocated to CEF arm. TLE3+ CEF=patients with ⩾30% TLE3 tumour-positive cells allocated to CEF arm. TLE− EC/T=patients with <30% TLE3 tumour-positive cells allocated to EC/T arm. TLE3+ EC/T=patients with ⩾30% TLE3 tumour-positive cells allocated to EC/T arm. (B) Recurrence-free survival for TLE3-positive cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm. (C) Recurrence-free survival for TLE3-negative cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4559832&req=5

fig1: Visually assessed TLE3 staining and outcome by treatment arm. (A) Recurrence-free survival by Visual TLE3: Status stratified by allocation to EC/T or CEF: TLE− CEF=patients with <30% TLE3 tumour-positive cells allocated to CEF arm. TLE3+ CEF=patients with ⩾30% TLE3 tumour-positive cells allocated to CEF arm. TLE− EC/T=patients with <30% TLE3 tumour-positive cells allocated to EC/T arm. TLE3+ EC/T=patients with ⩾30% TLE3 tumour-positive cells allocated to EC/T arm. (B) Recurrence-free survival for TLE3-positive cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm. (C) Recurrence-free survival for TLE3-negative cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm.

Mentions: There were no significant differences in RFS for those allocated EC/T or CEF by TLE3 status (Figure 1A; P=0.29), although TLE3+ patients allocated EC/T had directionally better RFS experience than patients with TLE3− tumours or than TLE3+/− patients allocated CEF. For TLE3+ patients (Figure 1B), the HR of EC/T to CEF was 0.82 (95% CI 0.54 to 1.24; P=0.34). Meanwhile, the outcome for TLE3− tumours is shown in Figure 1C: the HR of EC/T to CEF is 0.55 (95% CI 0.21 to 1.43; P=0.21). Exploratory investigations with quartile cut-points also indicated no significant univariate RFS differences for TLE3+ patients allocated EC/T or CEF (Supplementary Figure 3A, with first quartile cut-point, P=0.91; Supplementary Figure 3B, with median cut-point, P=0.91).


TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial
Visually assessed TLE3 staining and outcome by treatment arm. (A) Recurrence-free survival by Visual TLE3: Status stratified by allocation to EC/T or CEF: TLE− CEF=patients with <30% TLE3 tumour-positive cells allocated to CEF arm. TLE3+ CEF=patients with ⩾30% TLE3 tumour-positive cells allocated to CEF arm. TLE− EC/T=patients with <30% TLE3 tumour-positive cells allocated to EC/T arm. TLE3+ EC/T=patients with ⩾30% TLE3 tumour-positive cells allocated to EC/T arm. (B) Recurrence-free survival for TLE3-positive cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm. (C) Recurrence-free survival for TLE3-negative cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559832&req=5

fig1: Visually assessed TLE3 staining and outcome by treatment arm. (A) Recurrence-free survival by Visual TLE3: Status stratified by allocation to EC/T or CEF: TLE− CEF=patients with <30% TLE3 tumour-positive cells allocated to CEF arm. TLE3+ CEF=patients with ⩾30% TLE3 tumour-positive cells allocated to CEF arm. TLE− EC/T=patients with <30% TLE3 tumour-positive cells allocated to EC/T arm. TLE3+ EC/T=patients with ⩾30% TLE3 tumour-positive cells allocated to EC/T arm. (B) Recurrence-free survival for TLE3-positive cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm. (C) Recurrence-free survival for TLE3-negative cases by Visual TLE3: Status stratified by allocation to EC/T or CEF: CEF=patients allocated to CEF arm. EC/T=patients allocated to EC/T arm.
Mentions: There were no significant differences in RFS for those allocated EC/T or CEF by TLE3 status (Figure 1A; P=0.29), although TLE3+ patients allocated EC/T had directionally better RFS experience than patients with TLE3− tumours or than TLE3+/− patients allocated CEF. For TLE3+ patients (Figure 1B), the HR of EC/T to CEF was 0.82 (95% CI 0.54 to 1.24; P=0.34). Meanwhile, the outcome for TLE3− tumours is shown in Figure 1C: the HR of EC/T to CEF is 0.55 (95% CI 0.21 to 1.43; P=0.21). Exploratory investigations with quartile cut-points also indicated no significant univariate RFS differences for TLE3+ patients allocated EC/T or CEF (Supplementary Figure 3A, with first quartile cut-point, P=0.91; Supplementary Figure 3B, with median cut-point, P=0.91).

View Article: PubMed Central - PubMed

ABSTRACT

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 &#10878;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&lt;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.

No MeSH data available.