Background: Breast cancer (BC) is the most commonly diagnosed cancer worldwide, 91% diagnosed in early stages and 80% of them expressing estrogen receptor (ER +). It is known that distant late recurrence (DLR) represents about 50% of all relapses. Thus, identifying patients with a higher risk of DLR is a essential need in ER + BC, leading to a potential personalized management. Within this scope, CTS 5 (Clinical Treatment Score after 5 years) was developed as a simple clinical-pathological tool that aims to estimate the residual risk of distance recurrence after 5 years of endocrine therapy (ET).

Methodology: The validity of CTS5 was tested in a retrospective cohort. Patients diagnosed between 2005 and 2011 with early BC, ER+/HER2- tumors, alive and without recurrence within the first 5 years were selected. The primary endpoint was the time for distant late recurrence (DLR). Cox regression models were used to determine the prognostic value of CTS5 and to produce Kaplan-Meier curves with associated risks of DLR.

Results: A total of 797 women were included with a median follow-up of 105 months. According to the CTS5, 424 (53.2%), 239 (30.0%), and 134 (16.8%) patients were classified into the low-, intermediate-, and high-risk of DLR, respectively (table 1). CTS5 results were prognostic for DLR: patients with CTS5-high showed a fivefold relative risk of developing an DLR compared to patients with CTS5-low (HR, 5.1 IC95% [2.24-11.47], p <0.0001) (table 2). When assessing continuously, an one-point increase in CTS5 increased the relative risk of DLR by 87% (HR, 1,87 95% CI [1,324 - 2,632] p <0.0001). These results were confirmed when we stratified by age (age≤50 years vs. age>50 years).

Conclusion: Our results support its use in clinical practice as a predictor for patients with early-stage BC, ER +, and HER2- in real life. Besides, our study serves as a hypothesis generator for future confirmations through prospective studies. Thus, we will be able to assess, through prospective studies, whether the CTS5 can be used to personalize the patient's follow-up or even evaluate its usefulness in the decision to prolong or not ET. Such results would be extremely important, given the known difficulty in accessing genomic assays, especially in developing countries.

Table 1 Risk groups classifed according to the CTS5 and the clinicopathological characteristics

Factors No. (%)   P value Total 
 Low Intermediate High   
 424 (53.2) 239 (30.0) 134 (16.8)   
Age, years      
<50 175 (41.3) 100 (41.8) 47 (35.1) .383 322 (40.4) 
>50 249 (58.7) 139 (58.2) 87 (64.9)  475 (59.6) 
Number of the positive nodes      
389 (91.7) 133 (55.6) 12 (9.0) <.0001 534 (67.0) 
31 (7.3) 81 (33.5) 28 (20.9)  139 (17.4) 
2-3 2 (0.5) 21 (8.8) 41 (30.6)  64 (8.0) 
4-9 2 (0.5) 3 (1.7) 32 (23.9)  38 (4.8) 
9+ 0 (0.0) 1 (0.4) 21 (15.7)  22 (2.8) 
Histological grade      
88 (20.7) 25 (10.4) 7 (5.2) <.0001 120 (15.0) 
196 (46.2) 129 (48.5) 38 (28.4)  363 (45.6) 
140 (33.1) 85 (35.6) 89 (66.4)  314 (39.4) 
Tumor size, mm      
<10 193 (45.5) 9 (3.8) 3 (2.2) <.0001 205 (25.7) 
10-20 199 (47.0) 94 (39.3) 29 (21.6)  322 (40.4) 
20-30 22 (5.2) 82 (34.3) 41 (30.6)  145 (18.2) 
> 30 10 (2.3) 54 (22.6) 61 (45.5)  125 (15.7) 
Histological Type      
Ductal 342 (80.7) 207 (86.6) 112 (83.6) <.0001 661 (82.9) 
Tubular 57 (13.4) 21 (8.8) 17 (12.7)  95 (11.9) 
Others 25 (5.9) 11 (4.6) 5 (3.7)  41 (5.1) 
Chemotherapy      
Neoadjuvant 10 (2.4) 22 (9.2) 25 (18.7) <.0001 57 (7.2) 
Adjuvant 153 (36.1) 146 (61.1) 92 (68.7)  391 (49.1) 
Radiotherapy      
Yes 271 (63.9) 184 (77.0) 119 (88.8) <.0001 574 (72.0) 
No 153 (36.1) 55 (23) 15(11.2)  223 (28) 
Administered endocrine therapy      
5 years tamoxifen 183 (43.2) 66 (27.6) 29 (21.6) <.0001 278 (34.9) 
5 years used aromatase inhibitor 210 (49.5) 146 (61.1) 78 (58.2)  434 (54.4) 
> 5 years tamoxifen 20 (4.7) 18 (7.5) 19 (14.2)  57 (7.2) 
> 5 years used aromatase inhibitor 11 (2.6) 9 (3.8) 8 (6.0)  28 (3.5) 
ET time, years      
393 (92.7) 212 (88.7) 107 (79.9) <.0001 712 (89.3) 
7 - 10 31 (7.3) 27 (11.3) 27 (20.1)  85 (10.7) 
Vital status      
Alive 420 (99.1) 236 (98.7) 128 (95.5) .016 784 (98.3) 
Dead 4 (0.9) 3 (1.3) 6 (4.5)  13 (1.7) 
Distant recurrence      
No 415 (97.9) 222 (92.9) 118 (88.1) <.0001 755 (94.7) 
Yes 9 (2.1) 17 (7.1) 16 (11.9)  42 (5.3) 
Factors No. (%)   P value Total 
 Low Intermediate High   
 424 (53.2) 239 (30.0) 134 (16.8)   
Age, years      
<50 175 (41.3) 100 (41.8) 47 (35.1) .383 322 (40.4) 
>50 249 (58.7) 139 (58.2) 87 (64.9)  475 (59.6) 
Number of the positive nodes      
389 (91.7) 133 (55.6) 12 (9.0) <.0001 534 (67.0) 
31 (7.3) 81 (33.5) 28 (20.9)  139 (17.4) 
2-3 2 (0.5) 21 (8.8) 41 (30.6)  64 (8.0) 
4-9 2 (0.5) 3 (1.7) 32 (23.9)  38 (4.8) 
9+ 0 (0.0) 1 (0.4) 21 (15.7)  22 (2.8) 
Histological grade      
88 (20.7) 25 (10.4) 7 (5.2) <.0001 120 (15.0) 
196 (46.2) 129 (48.5) 38 (28.4)  363 (45.6) 
140 (33.1) 85 (35.6) 89 (66.4)  314 (39.4) 
Tumor size, mm      
<10 193 (45.5) 9 (3.8) 3 (2.2) <.0001 205 (25.7) 
10-20 199 (47.0) 94 (39.3) 29 (21.6)  322 (40.4) 
20-30 22 (5.2) 82 (34.3) 41 (30.6)  145 (18.2) 
> 30 10 (2.3) 54 (22.6) 61 (45.5)  125 (15.7) 
Histological Type      
Ductal 342 (80.7) 207 (86.6) 112 (83.6) <.0001 661 (82.9) 
Tubular 57 (13.4) 21 (8.8) 17 (12.7)  95 (11.9) 
Others 25 (5.9) 11 (4.6) 5 (3.7)  41 (5.1) 
Chemotherapy      
Neoadjuvant 10 (2.4) 22 (9.2) 25 (18.7) <.0001 57 (7.2) 
Adjuvant 153 (36.1) 146 (61.1) 92 (68.7)  391 (49.1) 
Radiotherapy      
Yes 271 (63.9) 184 (77.0) 119 (88.8) <.0001 574 (72.0) 
No 153 (36.1) 55 (23) 15(11.2)  223 (28) 
Administered endocrine therapy      
5 years tamoxifen 183 (43.2) 66 (27.6) 29 (21.6) <.0001 278 (34.9) 
5 years used aromatase inhibitor 210 (49.5) 146 (61.1) 78 (58.2)  434 (54.4) 
> 5 years tamoxifen 20 (4.7) 18 (7.5) 19 (14.2)  57 (7.2) 
> 5 years used aromatase inhibitor 11 (2.6) 9 (3.8) 8 (6.0)  28 (3.5) 
ET time, years      
393 (92.7) 212 (88.7) 107 (79.9) <.0001 712 (89.3) 
7 - 10 31 (7.3) 27 (11.3) 27 (20.1)  85 (10.7) 
Vital status      
Alive 420 (99.1) 236 (98.7) 128 (95.5) .016 784 (98.3) 
Dead 4 (0.9) 3 (1.3) 6 (4.5)  13 (1.7) 
Distant recurrence      
No 415 (97.9) 222 (92.9) 118 (88.1) <.0001 755 (94.7) 
Yes 9 (2.1) 17 (7.1) 16 (11.9)  42 (5.3) 

Table 2. Survival analyses for DLR and Overall Survival in diferent subgroups (CTS5 as categorical)

Distance Late Recurrence
Low riskIntermediate risk HR (95% CI)pHigh risk HR (95% CI)p
All patients Reference 3.155 (1.406 - 7.080) .005 5.067 (2.239 - 11.467) < .0001 
>50 years old Reference 2.889 (1.049 - 7.952) .040 4.701 (1.737 - 12.723) .002 
<50 years old Reference 3.730 (.964 - 14.435) .057 5.494 (1.311 - 23.029) .02 
Overall Survival      
 Low risk Intermediate risk HR (95% CI) p High risk HR (95% CI) p 
All patients Reference 1.152 (.258 - 5.150) .853 3.948 (1.113 - 14.00) .034 
Distance Late Recurrence
Low riskIntermediate risk HR (95% CI)pHigh risk HR (95% CI)p
All patients Reference 3.155 (1.406 - 7.080) .005 5.067 (2.239 - 11.467) < .0001 
>50 years old Reference 2.889 (1.049 - 7.952) .040 4.701 (1.737 - 12.723) .002 
<50 years old Reference 3.730 (.964 - 14.435) .057 5.494 (1.311 - 23.029) .02 
Overall Survival      
 Low risk Intermediate risk HR (95% CI) p High risk HR (95% CI) p 
All patients Reference 1.152 (.258 - 5.150) .853 3.948 (1.113 - 14.00) .034 

Citation Format: Lucas Vian, Ronaldo Souza, Vladmir C. C. Lima, Daniella Y. T. Honda, Samara T. Pacheco, Caio D. Liz, Luciana B.M. Gomes, Bruno C. M. U. Júnior, Paula T. Guimarães, Celso S. S. Filho, Andréa P. Guimarães, Mauro D. S. Donadio, Angelo B.S. Fêde, Augusto O. Saito, Adriana R.G. Ribeiro, Joyce M. L. Maia, Iara K. F. Lustosa, Fabricio S. Castro, Monique C. Tavares, Marcelle G. Cesca, Marcelo Corassa, Noam F. Pondé, Solange Sanches. Validation of CTS5 as a predictor of distant late recurrence risk in HER2 negative luminal breast cancer: Latin American experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-63.