Time dependence of biomarkers: non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer

Research output: Contribution to journalArticlepeer-review


  • J. Stephen
  • G. Murray
  • D. A. Cameron
  • J. Thomas
  • I. H. Kunkler
  • W. Jack
  • G. R. Kerr
  • T. Piper
  • C. J H Van De Velde
  • A. Hasenburg
  • C. Markopoulos
  • L. Dirix
  • C. Seynaeve
  • J. M S Bartlett

External organisations

  • University of Edinburgh
  • Leiden University Medical Center - LUMC
  • University Hospital
  • Athens University
  • Oncology Center
  • Erasmus MC
  • Ontario Institute for Cancer Research


Background:We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial.Methods:The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years.Results:We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P


Original languageEnglish
Pages (from-to)2242-2247
Number of pages6
JournalBritish Journal of Cancer
Issue number12
Publication statusPublished - 9 Dec 2014


  • biomarkers, breast cancer, relapse risk, time dependency

ASJC Scopus subject areas

Sustainable Development Goals