Overestimation of Late Distant Recurrences in High-Risk Patients With ER-Positive Breast Cancer: Validity and Accuracy of the CTS5 Risk Score in the TEAM and IDEAL Trials

Research output: Contribution to journalArticlepeer-review


  • Iris Noordhoek
  • Erik J Blok
  • Elma Meershoek-Klein Kranenbarg
  • Hein Putter
  • Marjolijn Duijm-de Carpentier
  • Emiel J T Rutgers
  • Caroline Seynaeve
  • John M S Bartlett
  • Jean-Michel Vannetzel
  • Annette Hasenburg
  • Robert Paridaens
  • Christos J Markopoulos
  • Yasuo Hozumi
  • Johanneke E A Portielje
  • Judith R Kroep
  • Cornelis J H van de Velde
  • Gerrit-Jan Liefers

Colleges, School and Institutes

External organisations

  • Leiden University
  • Erasmus University Medical Center
  • Department of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, Netherlands; Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
  • Ontario Institute for Cancer Research
  • Department of Radiation Oncology, Gustave Roussy, Villejuif, France.
  • University Hospital Mainz, Mainz, Germany.
  • University Hospitals Leuven
  • National and Kapodistrian University of Athens
  • University of Tsukuba Hospital


PURPOSE: Most distant recurrences (DRs) in women with hormone receptor-positive breast cancer occur after 5 years from diagnosis. The Clinical Treatment Score post-5 years (CTS5) estimates DRs after 5 years of adjuvant endocrine therapy (AET). The aim of this study was to externally validate the CTS5 as a prognostic/predictive tool.

METHODS: The CTS5 categorizes patients who have been disease free for 5 years into low, intermediate, and high risk and calculates an absolute risk for developing DRs between 5 and 10 years. Discrimination and calibration were assessed using data from the TEAM and IDEAL trials. The predictive value of the CTS5 was tested with data from the IDEAL trial.

RESULTS: A total of 5,895 patients from the TEAM trial and 1,591 patients from the IDEAL trial were included. When assessing the CTS5 discrimination, significantly more DRs were found at 10 years after diagnosis in the CTS5 high- and intermediate-risk groups than in the low-risk group (hazard ratio, 5.7 [95% CI, 3.6 to 8.8] and 2.8 [95% CI, 1.7 to 4.4], respectively). In low- and intermediate-risk patients, the CTS5-predicted DR rates were higher, although not statistically significantly so, than observed rates. However, in high-risk patients, the CTS5-predicted DR rates were significantly higher than observed rates (29% v 19%, respectively; P < .001). The CTS5 was not predictive for extended AET duration.

CONCLUSION: The CTS5 score as applied to patients treated in the TEAM and IDEAL cohorts discriminates between risk categories but overestimates the risk of late DRs in high-risk patients. Therefore, the numerical risk assessment from the CTS5 calculator in its current form should be interpreted with caution when used in daily clinical practice, particularly in high-risk patients.


Original languageEnglish
Pages (from-to)JCO1902427
JournalJournal of Clinical Oncology
Publication statusE-pub ahead of print - 24 Jul 2020