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

J Clin Oncol. 2020 Oct 1;38(28):3273-3281. doi: 10.1200/JCO.19.02427. Epub 2020 Jul 24.


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.

Trial registration: ClinicalTrials.gov NCT00036270.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androstadienes / administration & dosage
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aromatase Inhibitors / administration & dosage
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / metabolism
  • Clinical Trials, Phase III as Topic
  • Cohort Studies
  • Female
  • Humans
  • Letrozole / administration & dosage
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Receptors, Estrogen / metabolism*
  • Reproducibility of Results
  • Risk Assessment / methods
  • Tamoxifen / administration & dosage


  • Androstadienes
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Receptors, Estrogen
  • Tamoxifen
  • Letrozole
  • exemestane

Associated data

  • ClinicalTrials.gov/NCT00036270