Abstract GS4-03: Validation of the clinical treatment score post 5 years (CTS5) in women with hormone receptor positive, HER2-negative, node-negative disease from the TAILORx study
Authors: Sestak Ivana , Crager Michael , Cuzick Jack , Dowsett Mitchell , Shak Steven , Tang Gong , Gray Robert , Sparano Joseph 
Published: March 2020

Background: The Clinical Treatment Score at 5 years (CTS5) is a prognostic tool using clinicopathological parameters (nodal status, tumor size, grade, and age) to estimate distant recurrence (DR) risk after 5 years of endocrine treatment for postmenopausal women with estrogen receptor (ER) positive breast cancer. It was developed and validated in the ATAC and BIG 1-98 trials. Here, we evaluate whether the CTS5 is prognostic in women who were distant recurrence (DR) free 5 years after adjuvant treatment who participated in the TAILORx study.

Methods: 10273 women with ER-positive, HER2-negative, and node-negative disease were entered into the TAILORx study and assigned or randomized to four treatment arms according to their Oncotype Recurrence Score (RS) (endocrine therapy alone (ET) or chemo-endocrine therapy (CET)). Primary endpoint of this analysis was DR and the primary objective of this analysis was to evaluate the CTS5 in the TAILORx study, stratified by chemotherapy use. Secondary objectives included validation of the CTS5 in two specific age groups (age≤50 years vs. age&gt;50 years) and in the four separate treatment arms. Cox regression models were used to determine the prognostic value of CTS5. Kaplan-Meier curves were used to estimate conditional 9-year DR risks (%). Hazard ratios are reported for an increase of 1-standard deviation of CTS5 in the overall analysis population.

Results: 7353 (71.6%) women were DR free 5 years after diagnosis with follow-up beyond 5 years, had information for all clinical parameters, and were included in this analysis. Median follow-up after 5 years was 2.9 years (1.8-3.9). Overall, mean age was 55.7 years (SD 9.0), mean tumor size 17.1mm (SD 7.8), and the vast majority had low or moderately differentiated disease (84.7%). CTS5 was significantly higher for women in arm D (RS 26-100, CET) compared to the other three arms (mean CTS5 3.09 vs. 2.82, P&lt;0.001). Overall, CTS5 was highly prognostic for late DR stratified for assigned chemotherapy arm (HR=1.57 (1.36-1.82), P&lt;0.0001) (Table). 5385 (72.9%) of women were categorised into the low risk group by CTS5, 1836 (25.0%) into the intermediate risk group, and 132 (2.1%) into the high risk group. Looking at each arm separately, CTS5 did not predict late DR in women with RS 0-10 and ET (arm A), but provided strong prognostic information for late DR in arms B (RS 11-25, ET), C (RS 11-25, CET), and D (RS 26-100, CET) (Table). CTS5 strongly predicted late DR in women who were older than 50 years (HR=1.78 (1.48-2.14), P&lt;0.0001), but to a smaller extent in women aged 50 years or younger (HR=1.35 (1.01-1.82), P=0.046) (Table).

Conclusions: Low risks of late DR of 3.1% (2.4-4.0) for RS scores 0-25 (ET) and 3.8% (2.9-4.8) for RS scores 11-100 (CET) were observed in this ER-positive, HER2-negative and node negative TAILORx cohort. We confirm the prognostic ability of the CTS5 for late DR in the TAILORx cohort, specifically for patients older than 50 years and/or those who were deemed intermediate or high risk by Oncotype Dx RS (11-100). Our results show that the CTS5 is less prognostic for late DR in women aged 50 years or younger who received 5 years of endocrine therapy only. Further evaluation of the CTS5 in premenopausal cohorts is needed before it can be applied to younger patients.

Table: Hazard Ratios (95% CI) for prognostic value of CTS5 overall and according to sub-groups.HR (95% CI )P-valueAll (N=7353)1.57 (1.36-1.82)&lt;0.0001Arm A (N=1323)1.34 (0.87-2.07)0.19Arm B (N=2746)1.50 (1.17-1.93)0.002Arm C (N=2655)1.56 (1.22-1.98)0.0003Arm D (N=629)1.90 (1.23-2.92)0.004Age ≤ 50 years (N=2259)1.35 (1.01-1.82)0.046Age &gt; 50 years (N=5094)1.78 (1.48-2.14)&lt;0.0001

Citation Format: Ivana Sestak, Michael Crager, Jack Cuzick, Mitchell Dowsett, Steven Shak, Gong Tang, Robert Gray, Joseph Sparano. Validation of the clinical treatment score post 5 years (CTS5) in women with hormone receptor positive, HER2-negative, node-negative disease from the TAILORx study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-03.