Abstract PS6-63: Validation of CTS5 as a predictor of distant late recurrence risk in HER2 negative luminal breast cancer: Latin American experience
Authors: Vian Lucas , Souza Ronaldo , Lima Vladmir C. C. , Honda Daniella Y. T. , Pacheco Samara T. , Liz Caio D. , Gomes Luciana B.M. , Júnior Bruno C. M. U. , Guimarães Paula T. , Filho Celso S. S. , Guimarães Andréa P. , Donadio Mauro D. S. , Fêde Angelo B.S. , Saito Augusto O. , Ribeiro Adriana R.G. , Maia Joyce M. L. , Lustosa Iara K. F. , Castro Fabricio S. , Tavares Monique C. , Cesca Marcelle G. , Corassa Marcelo , Pondé Noam F. , Sanches Solange 
Published: February 2021

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 &lt;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 &lt;0.0001). These results were confirmed when we stratified by age (age≤50 years vs. age&gt;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 characteristicsFactorsNo. (%)P valueTotalLowIntermediateHigh424 (53.2)239 (30.0)134 (16.8)Age, years&lt;50175 (41.3)100 (41.8)47 (35.1).383322 (40.4)&gt;50249 (58.7)139 (58.2)87 (64.9)475 (59.6)Number of the positive nodes0389 (91.7)133 (55.6)12 (9.0)&lt;.0001534 (67.0)131 (7.3)81 (33.5)28 (20.9)139 (17.4)2-32 (0.5)21 (8.8)41 (30.6)64 (8.0)4-92 (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 grade188 (20.7)25 (10.4)7 (5.2)&lt;.0001120 (15.0)2196 (46.2)129 (48.5)38 (28.4)363 (45.6)3140 (33.1)85 (35.6)89 (66.4)314 (39.4)Tumor size, mm&lt;10193 (45.5)9 (3.8)3 (2.2)&lt;.0001205 (25.7)10-20199 (47.0)94 (39.3)29 (21.6)322 (40.4)20-3022 (5.2)82 (34.3)41 (30.6)145 (18.2)&gt; 3010 (2.3)54 (22.6)61 (45.5)125 (15.7)Histological TypeDuctal342 (80.7)207 (86.6)112 (83.6)&lt;.0001661 (82.9)Tubular57 (13.4)21 (8.8)17 (12.7)95 (11.9)Others25 (5.9)11 (4.6)5 (3.7)41 (5.1)ChemotherapyNeoadjuvant10 (2.4)22 (9.2)25 (18.7)&lt;.000157 (7.2)Adjuvant153 (36.1)146 (61.1)92 (68.7)391 (49.1)RadiotherapyYes271 (63.9)184 (77.0)119 (88.8)&lt;.0001574 (72.0)No153 (36.1)55 (23)15(11.2)223 (28)Administered endocrine therapy5 years tamoxifen183 (43.2)66 (27.6)29 (21.6)&lt;.0001278 (34.9)5 years used aromatase inhibitor210 (49.5)146 (61.1)78 (58.2)434 (54.4)&gt; 5 years tamoxifen20 (4.7)18 (7.5)19 (14.2)57 (7.2)&gt; 5 years used aromatase inhibitor11 (2.6)9 (3.8)8 (6.0)28 (3.5)ET time, years5393 (92.7)212 (88.7)107 (79.9)&lt;.0001712 (89.3)7 - 1031 (7.3)27 (11.3)27 (20.1)85 (10.7)Vital statusAlive420 (99.1)236 (98.7)128 (95.5).016784 (98.3)Dead4 (0.9)3 (1.3)6 (4.5)13 (1.7)Distant recurrenceNo415 (97.9)222 (92.9)118 (88.1)&lt;.0001755 (94.7)Yes9 (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 RecurrenceLow riskIntermediate risk HR (95% CI)pHigh risk HR (95% CI)pAll patientsReference3.155 (1.406 - 7.080).0055.067 (2.239 - 11.467)&lt; .0001&gt;50 years oldReference2.889 (1.049 - 7.952).0404.701 (1.737 - 12.723).002&lt;50 years oldReference3.730 (.964 - 14.435).0575.494 (1.311 - 23.029).02Overall SurvivalLow riskIntermediate risk HR (95% CI)pHigh risk HR (95% CI)pAll patientsReference1.152 (.258 - 5.150).8533.948 (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.